P Chavan, Sachiko Chikahisa, Tetsuya Shiuchi, Noriyuki Shimizu, Junhel Dalanon, Kazuo Okura, Hiroyoshi Sei and Yoshizo Matsuka : Dual orexin receptor antagonist drug suvorexant can help in amelioration of predictable chronic mild stress-induced hyperalgesia, Brain Research Bulletin, Vol.188, 39-46, 2022.
(要約)
This study aimed to evaluate the involvement of the orexin system in predictable chronic mild stress (PCMS) and the effects of suvorexant, a dual orexin receptor antagonist, on nociceptive behavior in PCMS. Male C57BL/6 J mice were separated into various PCMS groups: a control group with sawdust on the floor of the rearing cage (C), a group with mesh wire on the floor (M), and a group with water just below the mesh wire (W). Activation of lateral hypothalamic orexin neurons was assessed using immunofluorescence. In another experiment, half of the mice in each group were administered an intraperitoneal injection of suvorexant (10 mg/kg), and the remaining mice were injected with the same amount of vehicle (normal saline). Thermal hyperalgesia was examined using tail immersion and hot plate tests, while mechanical hyperalgesia was investigated using the tail pinch test after 21 days of PCMS. Animals subjected to PCMS showed an increased percentage of activated orexin neurons in the lateral hypothalamic region after 21 days. Mice raised in the PCMS environment showed increased pain sensitivity in several pain tests; however, the symptoms were significantly reduced by suvorexant administration. The findings revealed that PCMS activates hypothalamic orexin neuronal activity, and the use of suvorexant can help attenuate PCMS-induced thermal and mechanical hyperalgesia.
Tetsuya Shiuchi, Airi Otsuka, Noriyuki Shimizu, Sachiko Chikahisa and Hiroyoshi Sei : Feeding Rhythm-Induced Hypothalamic Agouti-Related Protein Elevation via Glucocorticoids Leads to Insulin Resistance in Skeletal Muscle., International Journal of Molecular Sciences, Vol.22, No.19, 2021.
(要約)
Circadian phase shifts in peripheral clocks induced by changes in feeding rhythm often result in insulin resistance. However, whether the hypothalamic control system for energy metabolism is involved in the feeding rhythm-related development of insulin resistance is unknown. Here, we show the physiological significance and mechanism of the involvement of the agouti-related protein (AgRP) in evening feeding-associated alterations in insulin sensitivity. Evening feeding during the active dark period increased hypothalamic AgRP expression and skeletal muscle insulin resistance in mice. Inhibiting AgRP expression by administering an antisense oligo or a glucocorticoid receptor antagonist mitigated these effects. AgRP-producing neuron-specific glucocorticoid receptor-knockout (AgRP-GR-KO) mice had normal skeletal muscle insulin sensitivity even under evening feeding schedules. Hepatic vagotomy enhanced AgRP expression in the hypothalamus even during ad-lib feeding in wild-type mice but not in AgRP-GR-KO mice. The findings of this study indicate that feeding in the late active period may affect hypothalamic AgRP expression via glucocorticoids and induce skeletal muscle insulin resistance.
Daisuke Tanioka, Sachiko Chikahisa, Noriyuki Shimizu, Tetsuya Shiuchi, Noriaki Sakai, Seiji Nishino and Hiroyoshi Sei : Intracranial mast cells contribute to the control of social behavior in male mice., Behavioural Brain Research, Vol.403, 113143, 2021.
(要約)
Mast cells (MCs) exist intracranially and have been reported to affect higher brain functions in rodents. However, the role of MCs in the regulation of emotionality and social behavior is unclear. In the present study, using male mice, we examined the relationship between MCs and social behavior and investigated the underlying mechanisms. Wild-type male mice intraventricularly injected with a degranulator of MCs exhibited a marked increase in a three-chamber sociability test. In addition, removal of MCs in Mast cell-specific Toxin Receptor-mediated Conditional cell Knock out (Mas-TRECK) male mice showed reduced social preference levels in a three-chamber sociability test without other behavioral changes, such as anxiety-like and depression-like behavior. Mas-TRECK male mice also had reduced serotonin content and serotonin receptor expression and increased oxytocin receptor expression in the brain. These results suggested that MCs may contribute to the regulation of social behavior in male mice. This effect may be partially mediated by serotonin derived from MCs in the brain.
Yoshitsugu Kondoh, Sachiko Chikahisa, Tetsuya Shiuchi, Noriyuki Shimizu, Daisuke Tanioka, Haruo Uguisu and Hiroyoshi Sei : Sleep profile during fasting in PPAR-alpha knockout mice., Physiology & Behavior, Vol.214, 112760, 2020.
(要約)
Peroxisome proliferator-activated receptor alpha (PPARα) is a transcription factor that belongs to the nuclear receptor family and plays an important role in regulating gene expression associated with lipid metabolism. PPARα promotes hepatic fatty acid oxidation and ketogenesis in response to fasting. Because energy metabolism is known to affect sleep regulation, manipulations that change PPARα are likely to affect sleep and other physiological phenotypes. In this study, we examined the role of PPARα in sleep/wake regulation using PPARα knockout (KO) mice. Sleep, body temperature (BT), locomotor activity, arterial pressure (AP) and heart rate (HR) were recorded in KO mice and wild-type (WT) controls under ad libitum-fed conditions and 24-hour food deprivation (FD). KO and WT mice were identical in basal sleep amount, BT, mean AP and HR, although KO mice showed enhanced sleepiness (enhanced EEG slow-wave activity). In response to FD, KO mice showed a large drop in wakefulness and locomotor activity at the end of the dark phase, whereas WT mice did not. Similarly, AP and HR, which were suppressed by FD, decreased more in KO than in WT mice. Compared to WT mice, KO mice showed a reduced concentration of plasma ketone bodies and decreased mRNA expression of the ketogenic enzyme gene Hmgcs2 in the liver and brain under FD conditions. These results suggest that PPARα and/or lipid metabolism is involved in the maintenance of wakefulness and locomotor activity during fasting in mice.
Kazuhiro Muramatsu, Sachiko Chikahisa, Noriyuki Shimizu, Hiroyoshi Sei and Yuichi Inoue : Rotigotine suppresses sleep-related muscle activity augmented by injection of dialysis patients' sera in a mouse model of restless legs syndrome., Scientific Reports, Vol.9, No.1, 2019.
(要約)
Idiopathic restless legs syndrome (RLS) has a genetic basis wherein BTBD9 is associated with a higher risk of RLS. Hemodialysis patients also exhibit higher rates of RLS compared with the healthy population. However, little is known about the relationship of BTBD9 and end-stage renal disease to RLS pathophysiology. Here we evaluated sleep and leg muscle activity of Btbd9 mutant (MT) mice after administration of serum from patients with either idiopathic or RLS due to end-stage renal disease (renal RLS) and investigated the efficacy of treatment with the dopamine agonist rotigotine. At baseline, the amount of rapid eye movement (REM) sleep was decreased and leg muscle activity during non-REM (NREM) sleep was increased in MT mice compared to wild-type (WT) mice. Wake-promoting effects of rotigotine were attenuated by injection of serum from RLS patients in both WT and MT mice. Leg muscle activity during NREM sleep was increased only in MT mice injected with serum from RLS patients of ideiopatic and renal RLS. Subsequent treatment with rotigotine ameliorated this altered leg muscle activity. Together these results support previous reports showing a relationship between the Btbd9/dopamine system and RLS, and elucidate in part the pathophysiology of RLS.
Tetsuya Shiuchi, Takuya Masuda, Noriyuki Shimizu, Sachiko Chikahisa and Hiroyoshi Sei : Dopamine stimulation of the septum enhances exercise efficiency during complicated treadmill running in mice., The Journal of Physiological Sciences, Vol.69, No.6, 1019-1028, 2019.
(要約)
We aimed to identify the neurotransmitters and brain regions involved in exercise efficiency in mice during continuous complicated exercises. Male C57BL/6J mice practiced treadmill running with intermittent obstacles on a treadmill for 8 days. Oxygen uptake (VO
Tetsuya Shiuchi, Yumiko Miyatake, Airi Otsuka, Sachiko Chikahisa, Hiroshi Sakaue and Hiroyoshi Sei : Role of orexin in exercise-induced leptin sensitivity in the mediobasal hypothalamus of mice., Biochemical and Biophysical Research Communications, Vol.514, No.1, 166-172, 2019.
(要約)
Orexin is known as an important neuropeptide in the regulation of energy metabolism. However, the role of orexin in exercise-induced leptin sensitivity in the hypothalamus has been unclear. In this study, we determined the effect of transient treadmill exercise on leptin sensitivity in the mediobasal hypothalamus (MBH) of mice and examined the role of orexin in post-exercise leptin sensitivity. Treadmill running for 45min increased the orexin neuron activity in mice. Intraperitoneal injection of a submaximal dose of leptin after exercise stimulated the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in MBH of mice post-exercise compared with that in non-exercised mice, although intracerebroventricular (icv) injection of leptin did not enhance STAT3 phosphorylation, even after exercise. Icv injection of an orexin receptor antagonist, SB334867 reduced STAT3 phosphorylation, which was enhanced by icv injection of orexin but not by direct injection of orexin into MBH. Exercise increased the phosphorylation of extracellular signal-regulated kinases (ERKs) in the MBH of mice, while ERK phosphorylation was reduced by SB334867. Leptin injection after exercise increased the leptin level in MBH, whereas icv injection of SB334867 suppressed the increase in the leptin level in MBH of mice. These results indicate that the activation of orexin neurons by exercise may contribute to the enhancement of leptin sensitivity in MBH. This effect may be mediated by increased transportation of circulating leptin into MBH, with the involvement of ERK phosphorylation.
Airi Otsuka, Tetsuya Shiuchi, Sachiko Chikahisa, Noriyuki Shimizu and Hiroyoshi Sei : Sufficient intake of high-fat food attenuates stress-induced social avoidance behavior., Life Sciences, Vol.219, 219-230, 2019.
(要約)
Mice subjected to SDS ate either a high-fat or normal chow diet for 10 days. Behavioral tests were conducted following the completion of the SDS paradigm. The hypothalamus, liver, and blood were examined post-mortem.
Sachiko Chikahisa, Daiki Chida, Tetsuya Shiuchi, Saki Harada, Noriyuki Shimizu, Airi Otsuka, Daisuke Tanioka and Hiroyoshi Sei : Enhancement of fear learning in PPAR knockout mice., Behavioural Brain Research, Vol.359, 664--670, 2019.
(要約)
Peroxisome proliferator-activated receptor alpha (PPAR) is a member of the nuclear receptor superfamily and regulates fatty acid oxidation. Although PPAR is expressed not only in the peripheral tissues but also in the brain, its role in higher brain function is unclear. In this study, we investigated the role of PPAR in the control of behavior, including memory/learning and mood change, using PPAR knockout (KO) mice. A significant difference between wild-type (WT) and KO mice was seen in the passive avoidance test, demonstrating that KO mice showed enhanced fear leaning. In the amygdala of KO mice, the levels of dopamine and its metabolites were increased, and the mRNA expression of dopamine degrading enzyme was decreased. When dopamine D1 receptor antagonist was administered, the enhanced fear learning observed in KO mice was attenuated. These results suggest that PPAR is involved in the regulation of emotional memory via the dopamine pathway in the amygdala.
Sachiko Chikahisa, Saki Harada, Noriyuki Shimizu, Tetsuya Shiuchi, Airi Otsuka, Seiji Nishino and Hiroyoshi Sei : Mast cell involvement in glucose tolerance impairment caused by chronic mild stress with sleep disturbance., Scientific Reports, Vol.7, No.1, 2017.
(要約)
We have developed a chronic mild stress (MS) mouse model by simply rearing mice on a wire net for 3 weeks and investigated the effects of MS on glucose homeostasis and sleep. MS mice showed impaired glucose tolerance and disturbed sleep. One-week treatment with a histamine H1 receptor antagonist (H1RA) ameliorated the glucose intolerance and improved sleep quality in MS mice. MS mice showed an increased number of mast cells in both adipose tissue and the brain. Inhibition of mast cell function ameliorated the impairment in both glucose tolerance and sleep. Together, these findings indicate that mast cells may represent an important pathophysiological mediator in sleep and energy homeostasis.
Kanna Oura, Airi Otsuka, Tetsuya Shiuchi, Sachiko Chikahisa, Noriyuki Shimizu and Hiroyoshi Sei : Late feeding in the active period decreases slow-wave activity., Life Sciences, Vol.160, 18-26, 2016.
(要約)
Sleep and feeding behaviors closely interact to maintain energy homeostasis. While it is known that sleep disorders can lead to various metabolic issues such as insulin resistance, the mechanism for this effect is poorly understood. We thus investigated whether different feeding rhythms during the active period affect sleep-wake regulation. For 2weeks, mice were randomly assigned to 1 of 3 feeding schedules as follows: free access to lab chow during the active period (ZT12-24, Ad-lib group), free access to lab chow during the first half of the active period (ZT12-18; Morning group), or free access to lab chow during the second half of the active period (ZT18-24, Evening group). Food intake, body weight, body temperature, locomotor activity, and sleep were evaluated. The hypothalamus and cerebral cortex were examined post-mortem. No alterations in food intake or body weight were observed among the 3 groups. The Evening group showed lower slow-wave activity (SWA) than the other 2 groups, in addition to higher expression of orexin mRNA in the hypothalamus and higher concentrations of dopamine and its metabolites in the cerebral cortex. AMPK phosphorylation was increased in the hypothalamus of mice in the Evening group; however, AMPK inhibition had no effect on SWA. We concluded that late feeding reduces SWA in NREM sleep via a mechanism that involves orexin-mediated arousal in the hypothalamus and elevated monoamines in the cerebral cortex. These data have important implications for the relationship between sleep-wake disturbances and metabolic disorders.
Airi Otsuka, Tetsuya Shiuchi, Sachiko Chikahisa, Noriyuki Shimizu and Hiroyoshi Sei : Voluntary exercise and increased food intake after mild chronic stress improve social avoidance behavior in mice., Physiology & Behavior, Vol.151, 264-271, 2015.
(要約)
It is well-established that exercise can influence psychological conditions, cognitive function, and energy metabolism in peripheral tissues including the skeletal muscle. However, it is not clear whether exercise can influence social interaction with others and alleviate defeat stress. This study investigated the effect of voluntary wheel running on impaired social interaction induced by chronic social defeat stress (SDS) using the resident-intruder social defeat model. Mice were divided into three groups: control, stress alone, and stress+exercise. SDS was performed by exposing C57BL/6 mice to retired ICR mice for 2.5 min. The C57BL/6 mice were continuously defeated by these resident (aggressor) mice and, following 5 days of SDS, experienced 2 days of rest with no SDS. Mice in the stress+exercise group were allowed to voluntarily run on a wheel for 2h after every SDS exposure. Two weeks later, compared to the control group, the stress group showed a higher ratio of time spent in the corner zone of a social interaction paradigm even though SDS did not elicit depressive- and anxiety-like behaviors. We also observed that voluntary exercise, which did not affect muscle weight and gene expression, decreased social avoidance behavior of stressed mice without clear changes in brain monoamine levels. Interestingly, food intake in the stress+exercise group was the greatest among the three groups. To test the effect of the exercise-induced increase in food intake on social behavior, we set up a pair-fed group where food intake was restricted. We then compared these mice to mice in the stress alone group. We found that the ratio of time spent in the corner zone of the social interaction test was not different between ad libitum- and pair-fed groups, although pair-fed mice spent more time in the corner zone when an aggressor mouse was present than when it was absent. In addition, pair-feeding did not show exercise-induced reductions of adrenal gland weight and enhanced the loss of body fat. Our findings indicate that voluntary exercise reduces social avoidance behavior induced by SDS. Further, we determined that SDS and exercise-induced increases in food intake partially influence energy metabolism and social avoidance behavior.
Sachiko Chikahisa, Noriyuki Shimizu, Tetsuya Shiuchi and Hiroyoshi Sei : Ketone body metabolism and sleep homeostasis in mice., Neuropharmacology, Vol.79, 399-404, 2014.
(要約)
A link has been established between energy metabolism and sleep homeostasis. The ketone bodies acetoacetate and -hydroxybutyrate, generated from the breakdown of fatty acids, are major metabolic fuels for the brain under conditions of low glucose availability. Ketogenesis is modulated by the activity of peroxisome proliferator-activated receptor alpha (PPAR), and treatment with a PPAR activator has been shown to induce a marked increase in plasma acetoacetate and decreased -hydroxybutyrate in mice, accompanied by increased slow-wave activity during non-rapid eye movement (NREM) sleep. The present study investigated the role of ketone bodies in sleep regulation. Six-hour sleep deprivation increased plasma ketone bodies and their ratio (acetoacetate/-hydroxybutyrate) in 10-week-old male mice. Moreover, sleep deprivation increased mRNA expression of ketogenic genes such as PPAR and 3-hydroxy-3-methylglutarate-CoA synthase 2 in the brain and decreased ketolytic enzymes such as succinyl-CoA: 3-oxoacid CoA transferase. In addition, central injection of acetoacetate, but not -hydroxybutyrate, markedly increased slow-wave activity during NREM sleep and suppressed glutamate release. Central metabolism of ketone bodies, especially acetoacetate, appears to play a role in the regulation of sleep homeostasis.
Yuki Hosono, Kazuyoshi Kitaoka, Ryo Urushihara, Hiroyoshi Sei and Yohsuke Kinouchi : Anxiety affects amplitudes of red and green color-elicited flash visual evoked potentials in humans, The Journal of Medical Investigation : JMI, Vol.61, No.1,2, 79-83, 2014.
(要約)
It has been reported that negative emotional changes and conditions affect the visual faculties of humans at the neural level. On the other hand, the effects of emotion on color perception in particular, which are based on evoked potentials, are unknown. In the present study, we investigated whether different anxiety levels affect the color information processing for each of 3 wavelengths by using flash visual evoked potentials (FVEPs) and State-Trait Anxiety Inventory. In results, significant positive correlations were observed between FVEP amplitudes and state or trait anxiety scores in the long (sensed as red) and middle (sensed as green) wavelengths. On the other hand, short-wavelength-evoked FVEPs were not correlated with anxiety level. Our results suggest that negative emotional conditions may affect color sense processing in humans.
Sachiko Chikahisa, Tohru Kodama, Atsushi Soya, Yohei Sagawa, Yuji Ishimaru, Hiroyoshi Sei and Seiji Nishino : Histamine from brain resident MAST cells promotes wakefulness and modulates behavioral states., PLoS ONE, Vol.8, No.10, e78434, 2013.
(要約)
Mast cell activation and degranulation can result in the release of various chemical mediators, such as histamine and cytokines, which significantly affect sleep. Mast cells also exist in the central nervous system (CNS). Since up to 50% of histamine contents in the brain are from brain mast cells, mediators from brain mast cells may significantly influence sleep and other behaviors. In this study, we examined potential involvement of brain mast cells in sleep/wake regulations, focusing especially on the histaminergic system, using mast cell deficient (W/W(v)) mice. No significant difference was found in the basal amount of sleep/wake between W/W(v) mice and their wild-type littermates (WT), although W/W(v) mice showed increased EEG delta power and attenuated rebound response after sleep deprivation. Intracerebroventricular injection of compound 48/80, a histamine releaser from mast cells, significantly increased histamine levels in the ventricular region and enhanced wakefulness in WT mice, while it had no effect in W/W(v) mice. Injection of H1 antagonists (triprolidine and mepyramine) significantly increased the amounts of slow-wave sleep in WT mice, but not in W/W(v) mice. Most strikingly, the food-seeking behavior observed in WT mice during food deprivation was completely abolished in W/W(v) mice. W/W(v) mice also exhibited higher anxiety and depression levels compared to WT mice. Our findings suggest that histamine released from brain mast cells is wake-promoting, and emphasizes the physiological and pharmacological importance of brain mast cells in the regulation of sleep and fundamental neurobehavior.
Kazuyoshi Kitaoka, Noriyuki Shimizu, Koji Ono, Sachiko Chikahisa, Madoka Nakagomi, Koichi Shudo, Kazunori Ishimura, Hiroyoshi Sei and Kazuo Yoshizaki : The retinoic acid receptor agonist Am80 increases hippocampal ADAM10 in aged SAMP8 mice, Neuropharmacology, Vol.72, 58-65, 2013.
(要約)
The retinoic acid (RA, a vitamin A metabolite) receptor (RAR) is a transcription factor. Vitamin A/RA administration improves the Alzheimer's disease (AD)- and age-related attenuation of memory/learning in mouse models. Recently, a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) was identified as a key molecule in RA-mediated anti-AD mechanisms. We investigated the effect of chronic administration of the RAR agonist Am80 (tamibarotene) on ADAM10 expression in senescence-accelerated mice (SAMP8). Moreover, we estimated changes in the expression of the amyloid precursor protein (APP), amyloid beta (Aβ), and hairy/enhancer of split (Hes), which are mediated by ADAM10. Spatial working memory and the levels of a hippocampal proliferation marker (Ki67) were also assessed in these mice. ADAM10 mRNA and protein expression was significantly reduced in the hippocampus of 13-month-old SAMP8 mice; their expression improved significantly after Am80 administration. Further, after Am80 administration, the expression levels of Hes5 and Ki67 were restored and the deterioration of working memory was suppressed, whereas APP and Aβ levels remained unchanged. Our results suggest that Am80 administration effectively improves dementia by activating the hippocampal ADAM10-Notch-Hes5 proliferative pathway.
Nutritional state in the gestation period influences fetal growth and development. We hypothesized that undernutrition during gestation would affect offspring sleep architecture and/or homeostasis. Pregnant female mice were assigned to either control (fed ad libitum; AD) or 50% dietary restriction (DR) groups from gestation day 12 to parturition. After parturition, dams were fed AD chow. After weaning, the pups were also fed AD into adulthood. At adulthood (aged 8-9 weeks), we carried out sleep recordings. Although offspring mice displayed a significantly reduced body weight at birth, their weights recovered three days after birth. Enhancement of electroencephalogram (EEG) slow wave activity (SWA) during non-rapid eye movement (NREM) sleep was observed in the DR mice over a 24-hour period without changing the diurnal pattern or amounts of wake, NREM, or rapid eye movement (REM) sleep. In addition, DR mice also displayed an enhancement of EEG-SWA rebound after a 6-hour sleep deprivation and a higher threshold for waking in the face of external stimuli. DR adult offspring mice exhibited small but significant increases in the expression of hypothalamic peroxisome proliferator-activated receptor (Ppar) and brain-specific carnitine palmitoyltransferase 1 (Cpt1c) mRNA, two genes involved in lipid metabolism. Undernutrition during pregnancy may influence sleep homeostasis, with offspring exhibiting greater sleep pressure.
A Genshiro Sunagawa, Hiroyoshi Sei, Shigeki Shimba, Yoshihiro Urade and R Hiroki Ueda : FASTER: an unsupervised fully automated sleep staging method for mice., Genes to Cells, Vol.18, No.6, 502-518, 2013.
(要約)
Identifying the stages of sleep, or sleep staging, is an unavoidable step in sleep research and typically requires visual inspection of electroencephalography (EEG) and electromyography (EMG) data. Currently, scoring is slow, biased and prone to error by humans and thus is the most important bottleneck for large-scale sleep research in animals. We have developed an unsupervised, fully automated sleep staging method for mice that allows less subjective and high-throughput evaluation of sleep. Fully Automated Sleep sTaging method via EEG/EMG Recordings (FASTER) is based on nonparametric density estimation clustering of comprehensive EEG/EMG power spectra. FASTER can accurately identify sleep patterns in mice that have been perturbed by drugs or by genetic modification of a clock gene. The overall accuracy is over 90% in every group. 24-h data are staged by a laptop computer in 10 min, which is faster than an experienced human rater. Dramatically improving the sleep staging process in both quality and throughput FASTER will open the door to quantitative and comprehensive animal sleep research.
T Ogawa, Hiroyoshi Sei, H Konishi, N Shishioh-Ikejima and H Kiyama : The absence of somatotroph proliferation during continuous stress is a result of the lack of extracellular signal-regulated kinase 1/2 activation., Journal of Neuroendocrinology, Vol.24, No.10, 1335-1345, 2012.
(要約)
The integrity of homeostasis can be affected by chronic stress, and hyposomatotropism is evident in chronic stress-associated illnesses. In the present study, we demonstrated that a continuous stress (CS) severely affected somatotrophs among hormone-secreting cells in the anterior lobe (AL) of the pituitary by using a rat CS model. Among AL cells, the proliferation of somatotrophs was almost entirely suppressed in rats that had 3-5 days of CS (5dCS), although other hormone-secreting cells continued to proliferate. The cell size of somatotrophs was reduced at 5dCS (P<0.01), the number of secretory granules was increased at 3dCS (P<0.01) and serum growth hormone (GH) was on declining trend during 1 to 5dCS, suggesting that GH release was inhibited. GH-releasing hormone (GHRH) mRNA level in the arcuate nucleus was transiently decreased, whereas its receptor expression in the AL was significantly increased in CS rats. When 5dCS rats were injected with GHRH, transient GH secretion was observed, whereas proliferation of somatotrophs did not occur. The GHRH administration failed to stimulate extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and the nuclear translocation of ERK in somatotrophs. These results suggest that somatotrophs of 5dCS rats expressed sufficient GHRH receptor, which could transfer a signal for GH release. However, the GHRH-induced proliferation signal was blocked somewhere between the receptor and ERK1/2. Because significant increase of corticosterone in the initial stage (the 1-3dCS) was observed in this model, the corticosterone may affect the signalling. Although the mechanism underlying the blockage of the proliferation signal in somatotrophs under CS remains unclear, these somatotrophic disorder, suggesting that the present animal model may be useful for understanding the molecular mechanisms of chronic stress-associated illnesses.
(キーワード)
Animals / Blotting, Western / Cell Proliferation / Chronic Disease / Corticosterone / Enzyme Activation / Growth Hormone / Growth Hormone-Releasing Hormone / Immunohistochemistry / In Situ Hybridization / Male / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Phosphorylation / Pituitary Gland, Anterior / Protein Transport / Radioimmunoassay / Rats / Rats, Sprague-Dawley / Real-Time Polymerase Chain Reaction / Somatotrophs / Stress, Psychological
Hiroyoshi Sei : Blood pressure surges in REM sleep: A mini review., Pathophysiology, Vol.19, No.4, 233-241, 2012.
(要約)
Blood pressure displays large fluctuations during REM sleep, a period when skeletal muscle loses activity systemically. Blood pressure rises spontaneously in spike-like surges even with no body movement. The mechanism underlying this unique characteristic of cardiovascular control during REM sleep remains unclear. Where does the source for this blood pressure surge during REM sleep exist? Is it related to dreaming, which is one of the primary characteristics of REM sleep? Are peripheral mechanisms involved in this phenomenon? Here, evidence related to the above-mentioned questions is reviewed.
Sachiko Chikahisa and Hiroyoshi Sei : The role of ATP in sleep regulation., Frontiers in Neurology, Vol.2, 87, 2011.
(要約)
One of the functions of sleep is to maintain energy balance in the brain. There are a variety of hypotheses related to how metabolic pathways interact with sleep/wake regulation. A major finding that demonstrates an interaction between sleep and metabolic homeostasis is the involvement of adenosine in sleep homeostasis. An accumulation of adenosine is supplied from ATP, which can act as an energy currency in the cell. Extracellularly, ATP can act as an activity-dependent signaling molecule, especially in regard to communication between neurons and glia, including astrocytes. Furthermore, the intracellular AMP/ATP ratio controls the activity of AMP-activated protein kinase, which is a potent energy regulator and is recently reported to play a role in the regulation of sleep homeostasis. Brain ATP may support multiple functions in the regulation of the sleep/wake cycle and sleep homeostasis.
Kazuyoshi Kitaoka, Mika Shimizu, Noriyuki Shimizu, Sachiko Chikahisa, Madoka Nakagomi, Koichi Shudo, Kazuo Yoshizaki and Hiroyoshi Sei : Retinoic acid receptor antagonist LE540 attenuates wakefulness via the dopamine D1 receptor in mice, Brain Research, Vol.1423, 10-16, 2011.
(要約)
Vitamin A is a common lipophilic vitamin, and its function is mainly mediated by the binding of its metabolite retinoic acid to retinoic acid receptors (RARs) and retinoid X receptors. Recently, it was reported that the expression of the RARb (an RAR subtype) gene determines the contribution of the delta oscillation in the sleep electroencephalogram (EEG) patterns in mice. We also reported that 4-week dietary deficiency of vitamin A (VAD) causes the attenuation of delta power in sleep and spontaneous activity in mice. However, our previous study could not clarify whether the attenuation of delta power by VAD is attributed to the suppression of RARs. To address this problem, we investigated whether the chronic administration of LE540 (30mg/kg/day), an antagonist of RARs, for 1 or 4weeks attenuated EEG delta power during sleep in mice. Consequently, 4-week LE540 administration induced a significant attenuation of wakefulness and delta power in non-rapid eye movement sleep. Western blot analysis revealed a significant decrease in the expression of dopamine D1 receptor (D1DR) in the striatum and tyrosine hydroxylase in the midbrain of mice that were administered LE540 for 4weeks. High-performance liquid chromatography analysis of striatal tissue revealed a significant decrease in the homovanillic acid/dopamine ratio. Meanwhile, dopamine levels did not change in these mice. Our results suggest that the 4-week antagonism of RARs induces the attenuation of delta power. However, the attenuation of delta power may be elicited indirectly by the decrease of wakefulness followed by the hypo-expression of dopamine receptors especially D1DR.
Noriyuki Shimizu, Sachiko Chikahisa, Kazuyoshi Kitaoka, Seiji Nishino and Hiroyoshi Sei : Refeeding after a 24-hour fasting deepens NREM sleep in a time-dependent manner., Physiology & Behavior, Vol.104, No.3, 480-487, 2011.
(要約)
Sleep/wake cycle is regulated by a variety of neuropeptides in the hypothalamus, a brain region that also regulates energy homeostasis and feeding behavior. Since circadian rhythms are affected by energy metabolism and feeding condition, we investigated whether changes in feeding regimen would influence sleep/wake parameters and body temperature. We monitored sleep and body temperature across three days of baseline (day 1), fasting (day 2), and refeeding (day 3) conditions under ordinary ambient temperature and employed different refeeding schedules. Refeeding at ZT1 following the 24-h fasting enhanced EEG delta power in NREM sleep. However, when the time of refeeding was set at either ZT7 or ZT12, the enhancement of EEG delta power was attenuated. The amount of NREM sleep was not largely affected by a 24-h fasting started at ZT1, although fasting that started at ZT12 changed the temporal distribution of NREM sleep. Hypothalamic nNOS mRNA level was increased both before and after refeeding at ZT1 compared with control condition, while there was no significant change in mice refed at ZT7. Level of NPY mRNA in the arcuate nucleus was increased before the refeeding only at ZT1. These results suggest that refeeding after a 24-h fasting makes NREM sleep deeper in a time-dependent manner.
Yuta Yamamoto, Toshihito Tanahashi, Sakurako Katsuura, Ken Kurokawa, Kensei Nishida, Yuki Kuwano, Tomoko Kawai, Shigetada Teshima-Kondo, Sachiko Chikahisa, Yoshihiro Tsuruo, Hiroyoshi Sei and Kazuhito Rokutan : Interleukin-18 deficiency reduces neuropeptide gene expressions in the mouse amygdala related with behavioral change., Journal of Neuroimmunology, Vol.229, No.1-2, 129-139, 2010.
(要約)
In this study, we examined the effects of IL-18 deficiency on behaviors and gene expression profiles in 6 brain regions. IL-18(-/-) mice reduced depressive-like behavior and changed gene expressions predominantly in the amygdala compared with wild-type mice. Pathway analysis of the differentially expressed genes ranked behavior as the top-scored biological function. Of note, the absence of IL-18 decreased Avp, Hcrt, Oxt, and Pmch mRNA levels and the number of arginine vasopressin- and oxytocin-positive cells in the amygdala, but not in the hypothalamus. Our results suggest that IL-18-dependent vasopressinergic and oxytocinergic circuitry in the amygdala may regulate depressive-like behaviors in mice.
Shinya Ozaki, Kazunori Toida, Motohiko Suzuki, Yoshihisa Nakamura, Nobuaki Ohno, Taku Ohashi, Meiho Nakayama, Yuki Hamajima, Akira Inagaki, Kazuyoshi Kitaoka, Hiroyoshi Sei and Shingo Murakami : Impaired olfactory function in mice with allergic rhinitis., Auris, Nasus, Larynx, Vol.37, No.5, 575-583, 2010.
(要約)
OBJECTIVE: It has been reported that olfactory function is impaired in patients with allergic rhinitis. However, the mechanism of olfactory dysfunction in allergic rhinitis remains poorly understood. Because of difficulties in obtaining and analyzing human olfactory mucosa due to both technical and ethical issues, an animal model needs to be established to clarify the mechanism of olfactory dysfunction in allergic rhinitis. The purpose of this study was to study olfactory function and changes in olfactory mucosa using allergic rhinitis mice. METHODS: A model of allergic rhinitis mice with olfactory dysfunction was developed by sensitizing with ovalbumin (OVA), and intranasally challenging with the same allergen. Olfactory function of mice with or without allergic rhinitis was assessed by odor detection ability test with cycloheximide and local field potential (LFP) with 1-octanal. We also evaluated histological changes in the olfactory mucosa of allergic rhinitis mice by both light and electron microscopy. RESULTS: Both of odor detection ability test and LFP showed that olfactory function was impaired in mice with allergic rhinitis, but not in mice without allergic rhinitis. Histopathological findings showed prominent infiltration of eosinophils, plasma cells, neutrophils, mast cells, and macrophages in lamina propria of olfactory mucosa of mice with allergic rhinitis, although infiltration of these cells was not seen in control mice. Allergic rhinitis also increased the number and size of glands in olfactory mucosa, suggesting an elevated amount of mucin in olfactory mucosa. CONCLUSION: This study showed for the first time that mice with allergic rhinitis have impaired olfactory function, increased size and number of olfactory glands, and infiltration of eosinophils, neutrophils, mast cells, plasma cells, and macrophages in the olfactory mucosa. This suggests that allergic reactions are seen in olfactory mucosa of mice with allergic rhinitis, and that greater olfactory gland activity is associated with olfactory dysfunction. Also, this mouse model could provide an expedient system for analyzing mechanisms of olfactory dysfunction.
Kazuyoshi Kitaoka, Atsuko Sano, Sachiko Chikahisa, Kazuo Yoshizaki and Hiroyoshi Sei : Disturbance of rapid eye movement sleep in senescence-accelerated mouse prone/8 mice is improved by retinoic acid receptor agonist Am80 (Tamibarotene)., Neuroscience, Vol.167, No.3, 573-582, 2010.
(要約)
Senescence-accelerated mouse prone/8 (SAMP8) mice are known to exhibit age-related deterioration in sleep-wake architecture compared with senescence-accelerated mouse resistant/1 (SAMR1) mice. We investigated whether treatment with Am80 (Tamibarotene), a retinoic acid receptor agonist, would improve sleep in 9-10-month-old SAMP8 mice. One week of Am80 administration improved the decrease in rapid eye movement (REM) sleep shown by SAMP8 mice. Real-time RT-PCR analysis demonstrated an impairment in the hippocampal retinoid cascade (retinoic acid receptor alpha and transthyretin) in SAMP8 in comparison to SAMR1 mice. Am80 treatment induced an increase in mRNA expression in the vesicular acetylcholine transporter in the brainstem and transthyretin in the hippocampus. Furthermore, decreased cortical acetylcholine content in SAMP8 was improved by Am80 administration. Decreased non-REM sleep and delta oscillation were also observed in SAMP8 mice; however, this was not improved by Am80 administration. These results partially support the hypothesis that the effects of aging on sleep-wake architecture are improved by the activation of retinoic acid receptors. The improvement may be induced by the activation of the cholinergic pathway.
Katsutaka Oishi, Katsuhiko Sakamoto, Morichika Konishi, Yusuke Murata, Nobuyuki Itoh and Hiroyoshi Sei : FGF21 is dispensable for hypothermia induced by fasting in mice., Neuroendocrinology Letters, Vol.31, No.2, 198-202, 2010.
(要約)
Fibroblast growth factor 21 (FGF21) is a key metabolic regulator that is induced by peroxisome proliferator-activated receptor alpha (PPARalpha) activation in response to fasting. We recently reported that bezafibrate, a pan-agonist of PPARs, decreases body temperature late at night through hypothalamic neuropeptide Y (NPY) activation and others have shown that mice overexpressing FGF21 are prone to torpor.
(キーワード)
Animals / Body Temperature / Fasting / Fibroblast Growth Factors / Hypothalamus / Hypothermia / Ketogenic Diet / Liver / Male / Mice / Mice, Inbred C57BL / Mice, Knockout / Motor Activity / Neuropeptide Y / RNA, Messenger / Reverse Transcriptase Polymerase Chain Reaction
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20424589
Yuta Yamamoto, Toshihito Tanahashi, Tomoko Kawai, Sachiko Chikahisa, Sakurako Katsuura, Kensei Nishida, Shigetada Teshima-Kondo, Hiroyoshi Sei and Kazuhito Rokutan : Changes in behavior and gene expression induced by caloric restriction in C57BL/6 mice., Physiological Genomics, Vol.39, No.3, 227-235, 2009.
(要約)
Caloric restriction (CR) is an effective method for prevention of age-associated diseases as well as overweight and obesity; however, there is controversy regarding the effects of dieting regimens on behavior. In this study, we investigated two different dieting regimens: repeated fasting and refeeding (RFR) and daily feeding of half the amount of food consumed by RFR mice (CR). CR and RFR mice had an approximate 20% reduction in food intake compared with control mice. Open field, light-dark transition, elevated plus maze, and forced swimming tests indicated that CR, but not RFR, reduced anxiety- and depressive-like behaviors, with a reduction peak on day 8. Using a mouse whole genome microarray, we analyzed gene expression in the prefrontal cortex, amygdala, and hypothalamus. In addition to the CR-responsive genes commonly modified by RFR and CR, each regimen differentially changed the expression of distinct genes in each region. The most profound change was observed in the amygdalas of CR mice: 884 genes were specifically upregulated. Ingenuity pathway analysis revealed that these 884 genes significantly modified nine canonical pathways in the amygdala. alpha-Adrenergic and dopamine receptor signalings were the two top-scoring pathways. Quantitative RT-PCR confirmed the upregulation of six genes in these pathways. Western blotting confirmed that CR specifically increased dopamine- and cAMP-regulated phosphoprotein (Darpp-32), a key regulator of dopamine receptor signaling, in the amygdala. Our results suggest that CR may change behavior through altered gene expression.
(キーワード)
Amygdala / Animals / Behavior, Animal / Blotting, Western / Body Weight / Caloric Restriction / Dopamine and cAMP-Regulated Phosphoprotein 32 / Eating / Gene Expression Profiling / Male / Maze Learning / Mice / Mice, Inbred C57BL / Motor Activity / Oligonucleotide Array Sequence Analysis / Reverse Transcriptase Polymerase Chain Reaction / Signal Transduction / Swimming
Sachiko Chikahisa, Nobuhiro Fujiki, Kazuyoshi Kitaoka, Noriyuki Shimizu and Hiroyoshi Sei : Central AMPK contributes to sleep homeostasis in mice, Neuropharmacology, Vol.57, No.4, 369-374, 2009.
(要約)
AMP-activated protein kinase (AMPK) is an energy-sensing molecular signal involved in glucose and lipid metabolism. The known interaction of sleep with energy metabolism led us to investigate the role of central AMPK in sleep homeostasis. Sleep deprivation (SD) for 6 h increased p-AMPK protein in the hypothalamus and also increased the mRNA level of Ca(2+)/calmodulin (CaM)-dependent protein kinase kinase beta (CaMKK2), an activator of AMPK, and carnitine palmitoyltransferase 1 (CPT1), a downstream signaling factor of AMPK. Central injection of compound C (CC), an inhibitor of AMPK, suppressed EEG delta power during NREM sleep, while 5-aminoimidazole-4-carboxamide riboside (AICAR), an activator of AMPK, enhanced EEG delta power. The treatment of both CC and AICAR attenuated rebound responses of delta power in NREM sleep after SD. These results indicate that central AMPK is involved in the regulation of sleep depth and sleep homeostasis.
Tokiko Ogawa, Nobue Shishioh-Ikejima, Hiroyuki Konishi, Tetsuya Makino, Hiroyoshi Sei, Sumiko Kiryu-Seo, Masaaki Tanaka, Yasuyoshi Watanabe and Hiroshi Kiyama : Chronic stress elicits prolonged activation of alpha-MSH secretion and subsequent degeneration of melanotroph., Journal of Neurochemistry, Vol.109, No.5, 1389-1399, 2009.
(要約)
Prolonged stress affects homeostasis in various organs and induces stress-associated disorders. We examined the cellular changes of pituitary gland under the continuous stress condition using a rat model in which rats were kept in a cage filled with water to a height of 1.5 cm for up to 5 days. Among the pituitary hormone mRNAs, proopiomelanocortin mRNA was up-regulated specifically in the intermediate lobe (IL) of this rat model. Additionally, the peripheral blood levels of alpha-melanocyte stimulating hormone (alpha-MSH), a major product of proopiomelanocortin in IL were increased. The alpha-MSH secreting cells, melanotrophs, showed a markedly developed endoplasmic reticulum and Golgi apparatus in the early phase of the experiment. Subsequent continuous stress caused remarkable dilation of the endoplasmic reticulum, disruption of the Golgi structure, and the degeneration of some melanotrophs. In addition the dopaminergic nerve fibers from hypothalamus were markedly decreased in IL. A dopamine antagonist elicited the similar morphologic changes of melanotroph in normal rat. These findings suggest that prolonged stress suppressed hypothalamus-derived dopamine release in IL, which elicited over-secretion of alpha-MSH from the melanotrophs. The present study also suggests that prolonged hyperactivation of endocrine cells could lead to disorder of secretion mechanisms and eventual degeneration.
Kazuyoshi Kitaoka, Kaoru Uchida, Naoko Okamoto, Sachiko Chikahisa, Toshitsugu Miyazaki, Eiji Takeda and Hiroyoshi Sei : Fermented ginseng improves the first-night effect in humans, Sleep, Vol.32, No.3, 413-421, 2009.
(要約)
The goal of this study was to clarify whether ginseng fermented by lactic acid bacteria (fermented ginseng, FG), can improve the first-night effect (FNE) in humans. Behavioral tests and quantification of mRNA expression related to GABAergic neurotransmission in brain (glutamic acid decarboxylase 1, gamma-aminobutyrate aminotransferase [Abat], gamma-aminobutyric acid transporter 1 [GAT1], gamma-aminobutyric acid transporter 4, gamma-aminobutyric acid A receptor subunit alpha 1 and gamma-aminobutyric acid A receptor subunit alpha 2) were carried out in FG-treated mice. We also performed double-blind sleep recordings of human subjects given FG or placebo. A university-based sleep laboratory. Sixteen healthy male volunteers (aged 20.69 +/- 0.44 years) were observed in the human study. At the end of administration, 2 consecutive all-night polysomnography recordings were performed. Subjects also completed psychological questionnaires, and urine and saliva samples were taken to analyze stress-sensitive markers. The light-dark transition test demonstrated that FG had some anxiolytic effect in mice, but other anxiety measures were unaffected. The hippocampal mRNA expression showed a decrease of Abat and GAT1 suggesting an increase of GABA. Other regions (amygdala and cerebellum) showed no differences. Furthermore, there was some evidence (using simple pairwise comparisons but not supported in the full ANOVA model) that administration of FG tended to diminish decreases in total sleep time and sleep efficiency (seen as first night effects in the placebo group) without affecting sleep architecture. Our results suggest the administration of FG could improve the FNE in humans. The improvement may be related to an anxiolytic effect of FG which acts via GABAergic modification.
(キーワード)
睡眠 (sleep)
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19294962
Sachiko Chikahisa, Kumiko Tominaga, Tomoko Kawai, Kazuyoshi Kitaoka, Katsutaka Oishi, Norio Ishida, Kazuhito Rokutan and Hiroyoshi Sei : Bezafibrate, a PPARs agonist, decreases body temperature and enhances EEG delta oscillation during sleep in mice., Endocrinology, Vol.149, No.10, 5262-5271, 2008.
(要約)
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor family. PPARs play a critical role in lipid and glucose metabolism. We examined whether chronic treatment with bezafibrate, a PPAR agonist, would alter sleep and body temperature (BT). Mice fed with a control diet were monitored for BT, electroencephalogram (EEG), and electromyogram for 48 h under light-dark conditions. After obtaining the baseline recording, the mice were provided with bezafibrate-supplemented food for 2 wk, after which the same recordings were performed. Two-week feeding of bezafibrate decreased BT, especially during the latter half of the dark period. BT rhythm and sleep/wake rhythm were phase advanced about 2-3 h by bezafibrate treatment. Bezafibrate treatment also increased the EEG delta-power in nonrapid eye movement sleep compared with the control diet attenuating its daily amplitude. Furthermore, bezafibrate-treated mice showed no rebound of EEG delta-power in nonrapid eye movement sleep after 6 h sleep deprivation, whereas values in control mice largely increased relative to baseline. DNA microarray, and real-time RT-PCR analysis showed that bezafibrate treatment increased levels of Neuropeptide Y mRNA in the hypothalamus at both Zeitgeber time (ZT) 10 and ZT22, and decreased proopiomelanocortin-alpha mRNA in the hypothalamus at ZT10. These findings demonstrate that PPARs participate in the control of both BT and sleep regulation, which accompanied changes in gene expression in the hypothalamus. Activation of PPARs may enhance deep sleep and improve resistance to sleep loss.
Hiroyoshi Sei, Katsutaka Oishi, Sachiko Chikahisa, Kazuyoshi Kitaoka, Eiji Takeda and Norio Ishida : Diurnal amplitudes of arterial pressure and heart rate are dampened in Clock mutant mice and adrenalectomized mice., Endocrinology, Vol.149, No.7, 3576-3580, 2008.
(要約)
Arterial pressure (AP), heart rate (HR), and cardiovascular diseases, including ischemic heart attack and cerebrovascular accident, show diurnal variation. Evidence that circadian-related genes contribute to cardiovascular control has been accumulated. In this study, we measured the AP and HR of Clock mutant mice on the Jcl/ICR background to determine the role of the Clock gene in cardiovascular function. Mice with mutated Clock genes had a dampened diurnal rhythm of AP and HR, compared with wild-type control mice, and this difference disappeared after adrenalectomy. The diurnal acrophase in both mean arterial pressure and HR was delayed significantly in Clock mutant mice, compared with wild-type mice, and this difference remained after adrenalectomy. Clock mutant mice had a lower concentration of plasma aldosterone, compared with wild-type mice. Our data suggest that the adrenal gland is involved in the diurnal amplitude, but not the acrophase, of AP and HR, and that the function of the Clock gene may be related to the nondipping type of AP elevation.
Katsutaka Oishi, Naoki Ohkura, Hiroyoshi Sei, Juzo Matsuda and Norio Ishida : CLOCK regulates the circadian rhythm of kaolin-induced writhing behavior in mice., NeuroReport, Vol.18, No.18, 1925-1928, 2007.
(要約)
Kaolin-induced writhing reaction is a simple and convenient model of bradykinin-induced pain for assessment of analgesic actions. In this study, we demonstrated that the number of kaolin-induced writhing reaction was fluctuated in a circadian manner that peaked at the end of the resting period (dusk) and reduced during the active (dark) period in mice. Circadian rhythm of the writhing intensity was completely phase-shifted by a time-imposed restricted feeding. On the other hand, 24 h of food deprivation did not affect the writhing intensity, suggesting that the endogenous clock that can be entrained to the scheduled feeding is responsible to the circadian intensity of the writhing reaction. Day/night fluctuation of the writhing intensity was completely abolished and the writhing reaction was significantly reduced in the circadian clock deficient Clock-mutant mice, although the kaolin-induced bradykinin production and blood pressure suppression were not affected in these mutant mice. Our present study suggested that the circadian variation of the pain sensitivity is governed by the food-entrainable endogenous clock and by the circadian clock molecules in mammals.
Masamichi Kuwajima, Hiroaki Fujihara, Hiroyoshi Sei, Asako Umehara, Masako Sei, Tomi T. Tsuda, Akiko Sukeno, Tatsuya Okamoto, Akiko Inubushi, Yoichi Ueta, Toshio Doi and Hiroshi Kido : Reduced carnitine level causes death from hypoglycemia: possible involvement of suppression of hypothalamic orexin expression during weaning period., Endocrine Journal, Vol.54, No.6, 911-925, 2007.
(要約)
The mechanism of onset of hypoglycemia in patients with carnitine deficiency has yet to be determined. Using mice with systemic carnitine deficiency (JVS mice), we examined this mechanism, focusing on the weaning period (days 14-28 postpartum). For normal mice, the survival rate was 100%, and no hypoglycemia was observed at all. Gastric lactose began to decrease on day 17, and cellulose increased sharply in amount thereafter. For JVS mice, the survival rate was 77% on day 14 and 28% on day 28. From day 21 on, hypoglycemia was noted. Gastric lactose had disappeared almost completely by day 17, and cellulose was almost undetectable from days 14 to 28. Expression of orexin mRNA in the hypothalamus did not differ between JVS and normal mice on day 14, but was suppressed in JVS mice on days 21 and 28. When JVS mice were fed a carnitine-rich diet, suppression of expression of orexin mRNA in hypothalamus was eliminated, and on day 28 lactose and cellulose were detected in the stomach without hypoglycemia. In conclusion, the suppression of the expression of orexin in the hypothalamus during the weaning period may be involved in the marked anorexia in JVS mice, which eventually leads to death from hypoglycemia.
Miyazaki Koyomi, Wakabayashi Miyuki, Sachiko Chikahisa, Hiroyoshi Sei and Norio Ishida : PER2 controls circadian periods through nuclear localization in the suprachiasmatic nucleus, Genes to Cells, Vol.12, No.11, 1225-1234, 2007.
(要約)
Molecular circadian clock regulation engages a negative feedback loop comprising components of the negative limb, PERs and CRYs. In addition to the rhythmic transcriptional regulation of clock genes, controlled subcellular localization might contribute to the molecular mechanism of the mammalian circadian clock. To address this issue, we generated transgenic (TG) mice lines harboring either rat PER2 (rPER2) with a deleted nuclear localizing domain [NLD(-)] or intact PER2. In comparison with wild-type (WT) control, the period of the circadian locomotor rhythm in TG mice over-expressing NLD(-) PER2 was longer, while that in TG mice over-expressing intact PER2 was shorter. The nuclear entry of endogenous PER2, CRY1 and CRY2 was delayed in the suprachiasmatic nucleus (SCN) of NLD(-) PER2 TG mice under constant darkness, whereas that of mouse PER2 (mPER2) is accelerated in the SCN of intact PER2 TG mice. Under constant light, the locomotor activity of NLD(-) PER2 TG mice became arrhythmic, whereas WT animals remained rhythmic. These data indicate that PER2 controls circadian periods through nuclear localization in the SCN. In addition, sleep architecture was also affected in intact PER2 TG mice, suggesting PER2 can modulate a sleep molecular mechanism.
Kazuyoshi Kitaoka, Atsushi Hattori, Sachiko Chikahisa, Ken-ichi Miyamoto, Yutaka Nakaya and Hiroyoshi Sei : Vitamin A deficiency induces a decrease in EEG delta power during sleep in mice, Brain Research, Vol.1150, 121-130, 2007.
(要約)
Recent report (Maret, S., Franken, P., Dauvilliers, Y., Ghyselinck, N.B., Chambon, P., Tafti, M., 2005. Retinoic acid signaling affects cortical synchrony during sleep. Science 310, 111-113.) has suggested that vitamin A (retinol and its derivatives) is genetically involved in the electroencephalogram (EEG) delta oscillation during sleep. However, this finding has not yet been confirmed by other studies. In this study, we attempted to record the sleep EEG and behavior, and to quantify striatal monoamines in mice fed a vitamin A-deficient (VAD) diet for 4 weeks, in order to clarify the linkage between the delta oscillation and vitamin A. VAD mice demonstrated a significant decrease in the delta power of the EEG. However, 6-h sleep deprivation caused the recovery of the delta power in VAD mice to a level similar to that of the control. VAD also caused the decrease of spontaneous activity throughout 24-h period. Furthermore, dihydroxyphenylacetic acid, a metabolite of dopamine, was decreased significantly in the striatal tissue of VAD mice. Our present results suggest that the deficiency of vitamin A causes the attenuation of delta power in NREM sleep and spontaneous activity. These attenuations may be related to the alteration of striatal dopaminergic function.
(キーワード)
3,4-Dihydroxyphenylacetic Acid / Analysis of Variance / Animals / Behavior, Animal / Body Weight / Corpus Striatum / Delta Rhythm / Dopamine / Exploratory Behavior / Male / Mice / Mice, Inbred C57BL / Motor Activity / Serotonin / Sleep / Sleep Deprivation / Spectrum Analysis / Vitamin A / Vitamin A Deficiency
Sachiko Chikahisa, Atsuko Sano, Kazuyoshi Kitaoka, Ken-ichi Miyamoto and Hiroyoshi Sei : Anxiolytic effect of music depends on ovarian steroid in female mice., Behavioural Brain Research, Vol.179, No.1, 50-59, 2007.
(要約)
Music is known to be able to elicit emotional changes, including anxiolytic effects. The gonadal steroid hormones estradiol and progesterone have also been reported to play important roles in the modulation of anxiety. In the present study, we examined whether the effect of music on anxiety is related to ovarian steroid in female mice. Behavioral paradigms measuring anxiety were tested in gonadally intact (SHAM) and ovariectomized (OVX) female mice chronically treated with either placebo (OVX/Placebo), 17β-estradiol (OVX/E), or progesterone (OVX/P). In the elevated plus maze, light-dark transition, and marble burying tests, SHAM and OVX/P mice exposed to music showed less anxiety than those exposed to white noise or silence while OVX/placebo mice did not show these effects at all. OVX/E mice showed the anxiolytic effect of music only in the marble burying test. Furthermore, pretreatment with progesterone's metabolite inhibitor completely prevented the anxiolytic effect of music in behavioral tests, while pretreatment with a progesterone receptor blocker did not prevent the anxiolytic effect of music. These results suggest that exposure to music reduces anxiety levels, and ovarian steroids, mainly progesterone, may be involved in the anxiolytic effect of music observed in female mice.
(キーワード)
Anxiety / Music / 17β-estradio / Progesterone / Female mice
Sachiko Chikahisa, Hiroyoshi Sei, Masaki Morishima, Atsuko Sano, Kazuyoshi Kitaoka, Yutaka Nakaya and Yusuke Morita : Exposure to music in the perinatal period enhances learning performance and alters BDNF/TrkB signaling in mice as adults., Behavioural Brain Research, Vol.169, No.2, 312-319, 2006.
(要約)
Music has been suggested to have a beneficial effect on various types of performance in humans. However, the physiological and molecular mechanism of this effect remains unclear. We examined the effect of music exposure during the perinatal period on learning behavior in adult mice, and measured the levels of brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase receptor B (TrkB), which play critical roles in synaptic plasticity. In addition, we measured the levels of 3-phosphoinositide-dependent protein kinase-1 (PDK1) and mitogen-activated protein kinase (MAPK), downstream targets of two main pathways in BDNF/TrkB signaling. Music-exposed mice completed a maze learning task with fewer errors than the white noise-exposed mice and had lower levels of BDNF and higher levels of TrkB and PDK1 in the cortex. MAPK levels were unchanged. Furthermore, TrkB and PDK1 protein levels in the cortex showed a significant negative correlation with the number of errors on the maze. These results suggest that perinatal exposure of mice to music has an influence on BDNF/TrkB signaling and its intracellular signaling pathway targets, including PDK1, and thus may induce improved learning and memory functions.
Tadashi Wada, Hiroyoshi Sei, Kenji Kusumoto, Kazuyoshi Kitaoka, Sachiko Chikahisa, Kazuhito Rokutan and Yusuke Morita : Geranylgeranylacetone, an inducer of HSP 70, attenuates REM sleep rebound after sleep deprivation., Brain Research Bulletin, Vol.69, No.4, 388-392, 2006.
(要約)
The effect of pretreatment of geranylgeranylacetone (GGA), an inducer of heat shock protein (HSP) 70, on responses in sleep and core body temperature (Tcore) against sleep deprivation (SD) was examined in rats. After 3 days of GGA or vehicle injection, a 6-h period of SD was performed. During the recovery period, both rapid-eye movement (REM) and non-REM (NREM) sleep were increased in both GGA- and vehicle-injected rats. However, in GGA-injected rats, REM-sleep rebound was significantly suppressed, while NREM-sleep rebound remained unaffected. In addition, the increase of Tcore caused by SD was also attenuated in GGA-injected rats. In the hippocampus, both SD and the GGA pretreatment induced an increase in the expression of HSP70 mRNA, indicating that the SD functions as a stress for hippocampal neurons and that the GGA induces HSP70 expression. The findings suggest that pretreatment with GGA suppresses REM sleep rebound and the response of Tcore against SD.
Ryou Urushihara, Nagako Murase, C John Rothwell, Masafumi Harada, Yuki Hosono, Kotaro Asanuma, Hideki Shimazu, Kazumi Nakamura, Sachiko Chikahisa, Kazuyoshi Kitaoka, Hiroyoshi Sei, Yusuke Morita and Ryuji Kaji : Effect of repetitive transcranial magnetic stimulation applied over the premotor cortex on somatosensory-evoked potentials and regional cerebral blood flow., Neuroimage, Vol.31, No.2, 699-709, 2006.
(要約)
Somatosensory-evoked potentials (SEPs) are attenuated by movement. This phenomenon of 'gating' reflects sensorimotor integration for motor control. The frontal N30 component after median nerve stimulation was shown to be reduced in amplitude prior to hand movement. To investigate the mechanism of this sensory gating, we recorded median SEPs immediately before and after application of monophasic very low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS) of 250 stimuli over motor cortex (MC), premotor cortex (PMC), or supplementary motor area (SMA) in 9 healthy volunteers. The stimulus intensity for MC or PMC was set 85% of the resting motor threshold for the hand muscle, and that for SMA was at the active motor threshold for the leg muscle. SEPs showed significant increases in amplitudes of the frontal N30 component after PMC stimulation, but not after SMA or MC stimulation. Low-frequency (1 Hz) biphasic stimulation over PMC showed no significant N30 changes in 6 out of 9 subjects tested, indicating the effect being specific for 0.2 Hz monophasic stimulation. To examine the functional anatomy of the N30 change, single photon emission computed tomography was performed immediately before and after monophasic 0.2 Hz rTMS over PMC in all the 9 subjects. Regional cerebral blood flow showed significant increases mainly in PMC and prefrontal cortex, indicating the involvement of these cortical areas in sensory input gating for motor control.
Mie Sakata, Hiroyoshi Sei, Naomi Eguchi, Yusuke Morita and Yoshihiro Urade : Arterial Pressure and Heart Rate Increase during REM Sleep in Adenosine A2A-Receptor Knockout Mice, but not in Wild-Type Mice, Neuropsychopharmacology, Vol.30, No.10, 1856-1860, 2005.
(要約)
Rapid eye movement (REM)-sleep related changes in arterial pressure (AP) and heart rate (HR) were observed in homozygous and heterozygous adenosine A(2A) receptor (A2AR) knockout (KO) mice, and the corresponding wild-type mice. During REM sleep, the mean AP (MAP) and HR were clearly increased in the homozygous A2AR KO mice, while, in the wild-type mice, they were decreased or maintained at the same level. Neither homozygous nor heterozygous A2AR KO mice showed significant difference in diurnal pattern and the hourly values of MAP and HR compared to the wild-type mice. From these findings, it is likely that the adenosine A2AR is involved in autonomic regulation during REM sleep.
Hirofumi Hashimoto, Tatsushi Onaka, Makoto Kawasaki, Lei Chen, Takashi Mera, Atsushi Soya, Takeshi Saito, Hiroaki Fujihara, Hiroyoshi Sei, Yusuke Morita and Yoichi Ueta : Effects of cholecystokinin (CCK)-8 on hypothalamic oxytocin-secreting neurons in rats lacking CCK-A receptor, Autonomic Neuroscience : Basic & Clinical, Vol.121, No.1-2, 16-25, 2005.
(要約)
Peripheral administration of cholecystokinin (CCK)-8 selectively activates oxytocin (OXT)-secreting neurons in the supraoptic (SON) and the paraventricular nuclei (PVN) with the elevation of plasma OXT level in rats. We examined the effects of intravenous (iv) administration of CCK-8 on the neuronal activity of hypothalamic OXT-secreting neurons and plasma OXT level in Otsuka Long-Evans Tokushima Fatty (OLETF) rats that have a congenital defect in the expression of the CCK-A receptor gene. In situ hybridization histochemistry (ISH) for c-fos mRNA revealed that the expression of the c-fos gene was not induced in the SON, the PVN, the nucleus of the tractus solitarius (NTS) and the area postrema (AP) 30 min after iv administration of CCK-8 (20 and 40 microg/kg) in OLETF rats. In Long-Evans Tokushima Otsuka (LETO) rats (controls), c-fos mRNA was detected abundantly in those nuclei 30 min after iv administration of CCK-8 (20 microg/kg). Immunohistochemistry for c-fos protein (Fos) showed that the distributions of Fos-like immunoreactivity (LI) were identical to the results obtained from ISH. Dual immunostaining for OXT and Fos revealed that Fos-LI was mainly observed in OXT-secreting neurons in the SON and the PVN of LETO rats 90 min after iv administration of CCK-8 (20 microg/kg). Radioimmunoassay for OXT and arginine vasopressin (AVP) showed that iv administration of CCK-8 did not cause significant change in the plasma OXT and AVP levels in OLETF rats, while iv administration of CCK-8 caused a significant elevation of plasma OXT level without changing the plasma AVP level in LETO rats. These results suggest that peripheral administration of CCK-8 may selectively activate the hypothalamic OXT-secreting neurons and brainstem neurons through CCK-A receptor in rats.
(キーワード)
CCK-A receptor / Otsuka Long Evans Tokushima Fatty rat / Oxytocin / Paraventricular nucleus / Supraoptic nucleus
K Kitahama, S Araneda, M Geffard, Hiroyoshi Sei and H Okamura : Tyramine-immunoreactive neuronal structures in the rat brain: Abundance in the median eminence of the mediobasal hypothalamus, Neuroscience Letters, Vol.383, No.3, 215-219, 2005.
(要約)
Immunoreactivity to p-tyramine, one of the natural trace amines, was studied in the rat brain by an anti-p-tyramine antibody. Immunoreactivity to this amine is very weak in the nigrostriatal dopaminergic neurons and terminals, and weak in the locus coeruleus noradrenergic ones. It was intensified in these structures after monoamine oxidase inhibition. On the other hand, this amine was highly concentrated in the median eminence of the mediobasal hypothalamus, in which its physiological function on prolactin release has been demonstrated.
(キーワード)
Tyramine / Dopamine / Median eminence / Hypothalamus / Rat / 免疫組織化学 (immunohistochemistry)
Nociceptin (NOC), an endogenous ligand of the opioid receptor-like 1 receptor, is thought to be involved in learning and memory processes. Since acetylcholine (ACh) is involved in hippocampal function, and the hippocampus plays a critical role on the learning and memory function, hippocampal ACh release in NOC-receptor knockout mice was examined using an in vivo microdialysis method. The release of hippocampal ACh was largely increased in the knockout mice. Furthermore, in the knockout mice, an enhanced hippocampal theta rhythm, which is known to be linked to hippocampal memory function, was also observed. Immunohistochemically, in septum, co-existence of NOC receptor with cholinergic, but not with GABAergic neurons, was verified. The findings demonstrate that the NOC receptor is involved in hippocampal cholinergic function.
Kazuyoshi Kitaoka, Risa Ito, Hideo Araki, Hiroyoshi Sei and Yusuke Morita : Effect of mood state on anticipatory postural adjustments., Neuroscience Letters, Vol.370, No.1, 65-68, 2004.
(要約)
Static postural control has been demonstrated to link with psychological state. However, the effect of psychological state on dynamic postural control remains unclear. In this study, we examined the effect of mood state on anticipatory postural adjustment (APA), one of the most important functions for dynamic postural control. Fourteen healthy male subjects performed unilateral arm elevation tasks after completing a Profile of Mood States (POMS) questionnaire. Mood state measured by POMS and the latency or amplitude of the APA in the ventral muscles (rectus femoris, tibialis anterior) of the lower limb showed significant negative correlations. The correlation between the mood state and APA amplitude in the soleus was found to be significantly positive. There were significant negative correlations between the mood state and reaction-time. These findings suggest that it is possible that dynamic postural control is affected by mood state.
(キーワード)
Adaptation, Physiological / Adult / Affect / Electromyography / Humans / Male / Movement / Postural Balance / Posture / Psychomotor Performance / Questionnaires / Reaction Time
Kayoko Uezu, Hiroyoshi Sei, Atsuko Sano, Kazunori Toida, Toshiko Suzuki-Yamamoto, Takeshi Houtani, Tetsuo Sugimoto, Hiroshi Takeshima, Kazunori Ishimura and Yusuke Morita : Lack of nociceptin receptor alters body temperature during resting period in mice, NeuroReport, Vol.15, No.5, 751-755, 2004.
(要約)
The role of nociceptin (NOC) receptor on body core temperature (Tcore) control was examined using NOC receptor knockout mice. In homozygote NOC receptor-knockout, wild-type, and control C57BL/6J and 129/SV mice, Tcore was continuously recorded under 12:12 h light:dark (LD) and conditions of constant darkness (DD). The Tcore values during the resting period were higher in the NOC receptor-knockout mice than in both wild-type and control mice under both LD and DD conditions. Spontaneous activity during the resting period and plasma cortisol levels were not different between the NOC receptor-knockout and control mice. The findings herein indicate that the NOC receptor is involved in the control of Tcore during the resting period and is independent of light, physical activity and/or cortisol regulation.
Hiroaki Fujihara, Ryota Serino, Yoichi Ueta, Hiroyoshi Sei and Yusuke Morita : Six-hour selective REM sleep deprivation increases the expression of the galanin gene in the hypothalamus of rats., Brain Research. Molecular Brain Research, Vol.119, No.2, 152-159, 2003.
(要約)
The effect of short-term selective REM sleep deprivation (RSD) on the gene expression of galanin in the rat hypothalamus was examined using in situ hybridization histochemistry. Monitoring an electroencephalogram (EEG) and electromyogram (EMG) on an on-line computer screen, as the RSD rats entered REM sleep, they were gently stroked on their backs using a brush to wake them during the RSD period. Galanin mRNA levels in the preoptic area (POA) were significantly increased by RSD for a period of 6 h. RSD had no significant effect on the mRNA levels of corticotrophin-releasing factor (CRF), arginine vasopressin (AVP), oxytocin (OXT) or orexins. These results suggest that 6-h selective RSD may not be sufficient to induce the activation of the hypothalamo-pituitary adrenal axis, and that the expression of the galanin gene in the hypothalamus reacts more readily against the loss of REM sleep in comparison to other hypothalamic neuropeptides such as arginine vasopressin, oxytocin and orexins.
(キーワード)
Animals / Arginine Vasopressin / Carrier Proteins / Corticotropin-Releasing Hormone / Galanin / Hypothalamo-Hypophyseal System / 視床下部 (hypothalamus) / Intracellular Signaling Peptides and Proteins / Male / Neuropeptides / Oxytocin / Preoptic Area / RNA, Messenger / Rats / Rats, Wistar / Sleep Deprivation / Sleep, REM / Time Factors / Up-Regulation
Hiroyoshi Sei, Hiromi Sakata-Haga, Kyoko Ohta, Kazuhiko Sawada, Yusuke Morita and Yoshihiro Fukui : Prenatal exposure to alchol alters the light response in postnatal circadian rhythm, Brain Research, Vol.987, No.1, 131-134, 2003.
(要約)
We studied the effect of prenatal exposure to alcohol on later circadian rhythm in the rat. In the normal light-dark cycle, an 8-h phase advance brought forward the deep body temperature rhythm in control rats, although it had a smaller effect in prenatally ethanol-exposed rats. In long constant darkness, the phase response of the deep body temperature rhythm to a light pulse at the early subjective night was less marked in ethanol-exposed rats in comparison to controls. These results indicate that prenatal exposure to alcohol has a long-lasting effect on the light responsiveness of the deep body temperature circadian rhythm.
(キーワード)
Fetal alcohol syndrome / Circadian rhythm / Body temperature / Phase shift / Rat
Mariko Ochi, Shin Sono, Hiroyoshi Sei, Katsutaka Oishi, Hisato Kobayashi, Yusuke Morita and Norio Ishida : Sex difference in circadian period of body temperature in Clock mutant mice with Jcl/ICR background, Neuroscience Letters, Vol.347, No.3, 163-166, 2003.
(要約)
The period of circadian rhythm remains remarkably stable in both sexes under conditions of constant darkness. Several studies have indicated that gonadal hormones such as estradiol shorten the period of circadian rhythms. We observed that the free-running period of core body temperature is longer in male homozygous Clock mutant mice than in females, although this difference is not found in wild mice. Furthermore, a gonadectomy had no effect on the period of core body temperature in either sex. This suggests the existence of a sex-related difference of the mammalian circadian system, and that it is independent of peripheral gonadal regulations.
(キーワード)
Clock gene / Core body temperature / Sex difference / Circadian period
Hiroyoshi Sei, Hiroaki Fujihara, Yoichiro Ueta, Kyoji Morita, Kunio Kitahama and Yusuke Morita : Single eight-hour shift of light-dark cycle increases brain-derived neurotrophic factor protein levels in the rat hippocampus, Life Sciences, Vol.73, No.1, 53-59, 2003.
(要約)
We previously reported that an eight hour phase advance in the light-dark (LD) cycle increases sleep in rats. Brain-derived neurotrophic factor (BDNF) is suggested to be one of the sleep and circadian regulating factors. We have therefore observed the responses of BDNF protein in the hippocampus, cerebellum and brainstem under conditions of LD change. BDNF protein was quantitatively measured using an ELISA kit. Under an 8-h LD phase advance, the levels of hippocampal BDNF were significantly increased on the day of the phase change, while the levels in the cerebellum and brainstem remained constant. Plasma corticosterone levels were not largely affected. Thus, a single LD shift acutely affects hippocampal BDNF metabolism with no large stress response.
Hiroyoshi Sei, Atsuko Sano, K. Oishi, Hiroaki Fujihara, H. Kobayashi, N. Ishida and Yusuke Morita : Increase of hippocampal acetylcholine release at the onset of dark phase is suppressed in a mutant mice model of evening-type individuals., Neuroscience, Vol.117, No.4, 785-789, 2003.
(要約)
We have previously reported that clock mutant mice on Jcl:ICR background show about 2-h delayed circadian profiles in body temperature, spontaneous activity and sleep-wake rhythm, and that they appear to be useful as a model of evening-type of individual. Hippocampal acetylcholine (ACh) release which is positively correlated with attention, learning and memory shows a circadian variation. In this study, changes in hippocampal ACh release in transitional phase from light (rest) to dark (active) period in clock mutant mice were monitored using an in vivo microdialysis method. Compared with wild mice, the increase in hippocampal ACh in the first 2 h of the active period in the mutant mice was suppressed in parallel with peak frequency in electroencephalogram theta rhythm. The molecular basis of the circadian system appears to have a strong effect on hippocampal cholinergic function, and is probably associating with individual temporal differences in voluntary behavior, cognition, learning and/or memory performance.
Kyoji Morita, Aki Kuwada, Hiroaki Fujihara, Yusuke Morita and Hiroyoshi Sei : Changes in the expression of steroid metabolism-related genes in rat adrenal glands during selective REM sleep deprivation, Life Sciences, Vol.72, No.17, 1973-1982, 2003.
(要約)
Selective REM sleep deprivation was carried out under the conditions designed to minimize the adverse influence of environmental conditions and restricted movement, and the influence of REM sleep deprivation on adrenocortical steroid metabolism was investigated by measuring the steady-state levels of mRNAs encoding steroid metabolism-related genes, steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme cytochrome P450 (P450scc) and steroid 5alpha-reductase (5alpha-R), in rat adrenal glands. Selective REM sleep deprivation caused a significant decrease in StAR mRNA and an increase in 5alpha-R mRNA levels without any notable change in P450scc mRNA levels in the adrenal gland. In contrast, non-selective sleep disturbance, resulting in the partial reductions of non-REM and REM sleep, tended to increase both StAR and P450scc mRNA levels without any statistical significance. These results indicate that REM sleep deprivation by itself may affect the expression of steroid metabolism-related genes in the adrenal gland, suggesting a possible relation between REM sleep and adrenocortical steroid metabolism.
Somatosensory evoked potentials (SEPs) are attenuated or gated during movement. The mechanism for this includes both centrifugal gating of afferent input and competition with other afferents caused by the movement (peripheral gating). Using a paradigm in which the signal for triggering movement is the electric stimulus for SEPs, we studied the gating of SEPs after tibial nerve stimulation prior to foot movement, and compared it with that during counting task. Significant gating was found for P40 component, which distributed centrally and ipsilaterally to the side of the stimulation, whereas the contralateral N40 component showed no changes. Dissociated gating of P40 and N40 indicates multiple generators of these components, in contrast to the previous view of a single generator dipole projecting tangentially. Together with the previous findings in median SEPs, these gating phenomena should represent a general mechanism for sensori-motor integration in preparation for limb movement.
Kazuyoshi Kirima, Koichiro Tsuchiya, Hiroyoshi Sei, Toyoshi Hasegawa, Michiyo Shikishima, Yuki Motobayashi, Kyoji Morita, Masanori Yoshizumi and Toshiaki Tamaki : Evaluatin of systemic blood NO dynamics by EPR Spectoscopy: HbNO as an endogenous index of NO, American Journal of Physiology, Heart and Circulatory Physiology, Vol.285, No.2, H589-H596, 2003.
(要約)
The measurement of hemoglobin-nitric oxide (NO) adduct (HbNO) in whole blood by the electron paramagnetic resonance (EPR) method seems relevant for the assessment of systemic NO levels. However, ceruloplasmin and unknown radical species overlap the same magnetic field as that of HbNO. To reveal the EPR spectrum of HbNO, we then introduced the EPR signal subtraction method, which is based on the computer-assisted subtraction of the digitized EPR spectrum of HbNO-depleted blood from that of sample blood using the software. Rats were treated with N(omega)-nitro-L-arginine methyl ester (L-NAME; 120 mg. kg-1. day-1) for 1 wk to obtain HbNO-depleted blood. When this method was applied to the analysis of untreated fresh whole blood, the five-coordinate state of HbNO was observed. HbNO concentration in pentobarbital-anesthetized rats was augmented (change in [HbNO] = 1.6-5.5 microM) by infusion of L-arginine (0.2-0.6 g/kg) but not D-arginine. Using this method, we attempted to evaluate the effects of temocapril on HbNO dynamics in an L-NAME-induced rat endothelial dysfunction model. The oral administration of L-NAME for 2 wk induced a serious hypertension, and the HbNO concentration was reduced (change in [HbNO] = 5.7 microM). Coadministration of temocapril dose dependently improved both changes in blood pressure and the systemic HbNO concentration. In this study, we succeeded in measuring the blood HbNO level as an index of NO by the EPR HbNO signal subtraction method. We also demonstrated that temocapril improves abnormalities of NO dynamics in L-NAME-induced endothelial dysfunction rats using the EPR HbNO signal subtraction method.
Yoshimasa Koyama, Kazumi Takahashi, Hiroyoshi Sei, Tohru Kodama and Yukihiko Kayama : Cholinergic neurons in the brainstem are involved in the fluctuation of blood pressure during paradoxical sleep, Sleep and Biological Rhythms, Vol.1, No.2, 105, 2003.
Hiroaki Fujihara, Hiroyoshi Sei, Yusuke Morita, Yoichiro Ueta and Kyoji Morita : Short-term sleep disturbance enhances BDNF gene expression in rat hippocampus by acting as internal stressor, Journal of Molecular Neuroscience : MN, Vol.21, No.3, 223-232, 2003.
(要約)
Rats were subjected to nonselective sleep disturbance for short periods under conditions designed to minimize the adverse influence of external stresses, such as environmental conditions and restricted movement, and both brain-derived neurotrophic factor (BDNF) protein and its mRNA levels in the brain were then determined to investigate the influence of sleep disturbance itself on BDNF gene expression. Total sleep duration was partially but significantly reduced by disturbing the sleep/wake cycle for 1 and 2 h, gradually increased according to the time of disturbance, then returned to control levels at 6 h after the beginning of sleep disturbance. Under these conditions, the slight but significant elevation of corticotrophin-releasing factor (CRF) mRNA levels in the paraventricular nucleus (PVN) was observed at an early stage of the sleep disturbance period. Sleep disturbance induced the elevation of both BDNF protein and its mRNA levels in the hippocampus but not in the cerebellum or the brainstem, and the elevated BDNF mRNA expression in the hippocampus returned toward basal levels during the sleep recovery period when the rebound of sleep duration was observed. These findings suggest the possibility that short-term disturbance of the sleep/wake cycle and, hence, the partial reduction of non-REM sleep duration, might exert a potential influence on neuronal and/or glial cells as an internal stressor, resulting in the elevation of BDNF gene expression in rat hippocampus.
Hiromi Ohno, Ryo Urushihara, Hiroyoshi Sei and Yusuke Morita : REM sleep deprivation suppresses acquisition of classical eyeblink conditioning, Sleep, Vol.25, No.8, 877-881, 2002.
(要約)
The aim of this study was to investigate the issue of whether REM sleep is involved in implicit learning through the cerebellum-related neural circuit via the use of classical eyeblink conditioning (CEC). Subjects were divided into three groups: control (sleep without interruption), REM sleep deprivation (RD), and slow wave sleep (stage 3+4) deprivation (SD). The CEC was performed after 8 hours of ordinary nocturnal sleep or sleep disrupted at a selected sleep stage. A university-based sleep laboratory. Twenty-seven healthy volunteers (all men, aged 23.2+/-0.6 years). The CEC was measured after selective sleep deprivation or ordinary nocturnal sleep. The eyeblink reflex was conditioned using a classical delay conditioning paradigm. The conditioned response (CR) was determined by electromyography measurements of the orbicularis oculi muscles. The rate of appearance of the CR was compared among the three groups. Compared with the control subjects, RD subjects were significantly deficient in their capacity to acquire conditioned eyeblinks, while no difference was found among the SD subjects. This study suggests that RD suppresses the cerebellar function in CEC and that REM sleep is closely linked with the learning function in the cerebellum.
(キーワード)
sleep deprivation / classical eyeblink conditioning / cerebellum / REM sleep / slow wave sleep / human
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12489894
Hiroyoshi Sei, Atsuko Sano, Hiromi Ohno, Kazue Yamabe, Yasuhiko Nishioka, Saburo Sone and Yusuke Morita : Age-related changes in control of blood pressure and heart rate during sleep in the rat, Sleep, Vol.25, No.3, 279-285, 2002.
(要約)
The aim of this study was to determine age-related changes in the control of mean arterial pressure (MAP) and heart rate (HR) during sleep, and its relationship to the baroreflex in aging. MAP, HR, body temperature (TP), spontaneous activity (ACT), and sleeping/waking duration were monitored for 24 hours in groups of young (10-12 wk old) and old (23-24 mo old) rats. The sleep laboratory at the University of Tokushima. Subjects were 8 young (10-12 wk old) and 7 old (23-24 mo old) Wistar rats. Reflex control of HR was evaluated by examining various pressure responses to an intravenous bolus injection of phenylephrine and sodium nitroprusside. MAP and TP were recorded by a radiotelemetry system. HR was detected from the AP signal. ACT was counted by a photo-sensor system. In the case of old rats, the sensitivity of baroreflex control of HR was significantly depressed, and the spontaneous increase of MAP and HR during REM sleep and the MAP drop at the end of REM sleep were significantly enhanced. The old rats showed no large deterioration of the circadian profiles of MAP, HR, TP, and the amount of sleep. The baroreflex dysfunction is considered to appear in an early stage of the aging process, and to affect the control of MAP and HR during sleep.
Mie Sakata, Hiroyoshi Sei, Kazunori Toida, Hiroaki Fujihara, Ryo Urushihara and Yusuke Morita : Mesolimbic dopaminergic system is involved in diurnal blood pressure regulation, Brain Research, Vol.928, No.1-2, 194-201, 2002.
(要約)
Parkinson's disease (PD) patients with autonomic failure show no nocturnal decrease in blood pressure (BP). At present, it is not clear if this symptom is attributable to the disturbance of the dopaminergic (DA) system that is responsible for PD. In the present study, we determined that the mesolimbic DA system is involved in diurnal profiles of the mean BP (MBP) by destroying the A10 DA system in rats with 6-hydroxydopamine. In control rats, a clear dip in the MBP and heart rate (HR) occurs during the light, that is, resting period, analogous to the nocturnal dip in normal humans. This normal daytime decrease in MBP and HR was disturbed by inducing a lesion of the ventral tegmental area (VTA) DA neurons, although the rhythms of wake-sleep duration and behavioral activity remained relatively intact. On the basis of this evidence, the absence of a nocturnal dip in BP in PD patients is attributed to impairment of the mesolimbic DA system.
Kyoji Morita, Aki Kuwada, Hiroaki Fujihara, Yusuke Morita and Hiroyoshi Sei : Influence of sleep disturbance on steroid 5a-reductase mRNA levels in rat brain, Neuroscience, Vol.115, No.2, 341-348, 2002.
(要約)
Sleep deprivation has been shown to affect the production of steroid hormones in peripheral steroidogenic organs, but little is known about the influence of sleep disturbance on the metabolism of steroid hormones in the brain. To elucidate a possible association of the sleep-wake cycle with brain neurosteroid metabolism, the influence of short-term sleep disturbance on the expression of mRNA encoding steroid 5alpha-reductase, the enzyme converting progesterone and other steroid hormones to their neuroactive 5alpha-reduced metabolites, was investigated. Rats were first subjected to non-selective disturbance of the sleep-wake cycle, and the expression of steroid 5alpha-reductase mRNA in rat hippocampus and brainstem was determined using a semi-quantitative one-step RT-PCR technique. Non-selective disturbance of the sleep-wake cycle resulted in the elevation of 5alpha-reductase mRNA levels in the brainstem, but not in the hippocampus, and the elevated mRNA expression returned to the basal levels after a short period of the sleep recovery. Further studies showed that selective REM sleep deprivation significantly elevated 5alpha-reductase mRNA levels in both hippocampus and brainstem, thus proposing the possibility that REM sleep reduction may largely contribute to the elevation of steroid 5alpha-reductase mRNA levels observed during short-term disturbance of the sleep-wake cycle. Since the enhancement of steroid 5alpha-reductase gene expression may result in the elevation of neuroactive 5alpha-reduced steroid production in the brainstem, the findings presented here provide further evidence for suggesting that neuroactive steroids may play a physiologically important role in the neuronal network for REM sleep initiation and maintenance.
Kyoji Morita, Aki Kuwada, Atsuko Sano, Mie Sakata, Hiroyoshi Sei and Yusuke Morita : Semi-quantitative RT-PCR analysis of environmental influence on P450scc and PNMT mRNA expression in rat adrenal glands, Life Sciences, Vol.70, No.1, 73-80, 2001.
(要約)
Environmental influence on brain function, particularly spatial learning and memory, has been extensively investigated, but little is known about the influence of environmental conditions on the functions of peripheral organs. In the present study, the effects of different housing conditions on the steady-state levels of mRNAs encoding cholesterol side-chain cleavage enzyme (cytochrome P450scc) and phenylethanolamine N-methyltransferase (PNMT) in adrenal glands was examined to investigate the environmental influence on both adrenocortical and adrenomedullary functions. Behavioral changes of the animals housed in different conditions were first examined to assess the relevance of environmental manipulation used. In consistent with previous findings, housing of the animals in enriched conditions resulted in the significant reduction of spontaneous motor activity (locomotor activity and rearing) in comparison with housing in isolated conditions, thus indicating the relevance of housing conditions used in this work for investigating the environmental influence on adrenal function. Then, the effects of these housing conditions on P450scc and PNMT mRNA levels in adrenal glands were examined using semi-quantitative RT-PCR method. In comparison with the isolated group, the enriched group showed significantly higher levels of P450scc mRNA. In contrast, PNMT mRNA levels in the enriched group were significantly lower than those in the isolated group. These results propose the possibility that the environmental conditions may cause differential alterations in adrenocortical and adrenomedullary functions, although their possible association with behavioral changes still remains to be elucidated.
Hiroyoshi Sei, Katsutaka Oishi, Yusuke Morita and Norio Ishida : Mouse model for morningness/eveningness, NeuroReport, Vol.12, No.7, 1461-1464, 2001.
(要約)
Human morning/evening preferences has recently been reported to be associated with polymorphism of the 3' flanking region of the Clock gene, which was the first identified mammalian circadian clock gene. We recorded body temperature, spontaneous activity, electroencephalogram and electromyogram for 48 h in mice with Jcl:ICR genetic background and homozygous for the Clock mutation (Cl/Cl on Jcl:ICR). In both wild-type and Cl/Cl on Jcl:ICR, body temperature, activity, wake and sleep were completely entrained to LD cycle. However, phases of the rhythm for body temperature, activity and wake duration in the Cl/Cl on Jcl:ICR were about 2 h delayed in comparison with the wild-type. This study has provided further evidence on the close relationship between human morning/evening preference and the molecular basis of circadian clock system, and has suggested that Cl/Cl on Jcl:ICR is useful for an animal model for human morning/evening preference.
(キーワード)
body temperature / circadian / Clock gene / Mouse / sleep wake
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11388430
Hiroyoshi Sei, Daisuke Saitoh, Kei Yamamoto, Kyoji Morita and Yusuke Morita : Differential effect of short-term REM sleep deprivation on NGF and BDNF protein levels in the rat brain, Brain Research, Vol.877, No.2, 387-390, 2000.
(要約)
It is well known that REM sleep is associated with memory consolidation, especially, procedural skill learning. Neurotrophic factors are known to be involved in synaptic plasticity. We therefore investigated the effects of selective REM sleep deprivation (RSD) on NGF and BDNF proteins in the hippocampus, cerebellum and brainstem in the rat. NGF and BDNF were detected by an ELISA. Our findings show that 6 h RSD affected the NGF and BDNF protein levels in different manner. In the cerebellum and brainstem, BDNF was significantly decreased, while NGF was not changed. Conversely, in the hippocampus, NGF was significantly decreased while BDNF was not changed. This study indicates that REM sleep may be associated with the secretion of neurotrophic factors and thus contribute to the memory functions.
Masako Sei, Hiroyoshi Sei and Kenji Shima : Spontaneous activity, sleep, and body temperature in rats lacking the CCK-A receptor, Physiology & Behavior, Vol.68, No.1-2, 25-29, 1999.
68.
Hiroyoshi Sei, Yuseke Morita, Kiyoshi Tsunooka and Hironobu Morita : Sino-aortic denervation augments the increase in blood pressure seen during paradoxical sleep in the rat, Journal of Sleep Research, Vol.8, No.1, 45-50, 1999.
69.
Isao Fukunishi, Hiroyoshi Sei, Yusuke Morita and Richard H. Rahe : Sympathetic activity in alexithymics with mother's low care, Journal of Psychosomatic Research, Vol.46, No.6, 579-589, 1999.
Masako Sei, Hiroyoshi Sei and Kenji Shima : Spontaneous Activity,Sleep,and Dody Temperature in Rats Lacking the CCK-A Receptor, Physiology & Behavior, Vol.68, No.1-2, 25-29, 1999.
(要約)
Because of a genetic mutation, the Otsuka-Long-Evans-Tokushima Fatty (OLETF) rat, a model for human non-insulin-dependent diabetes mellitus (NIDDM), shows no expression of the CCK-A receptor gene. We investigated the spontaneous physical activity, sleep, and body temperature in young OLETF rats that had not yet developed diabetes mellitus, and compared these data with age-matched control LETO (non-diabetic strain, Long-Evans-Tokushima-Otsuka) rats. The amount of large movements during the dark phase for the OLETF rats was significantly less than that of control rats. Thus, the amounts of total daily large movement and the ratio of dark-to-light phase movement in the OLETF rats were less than those of control rats, although the amount of small movement was similar for both groups. The diurnal rhythm of body temperature was similar for both groups. In addition, the amount of and circadian rhythm for each vigilance state and slow-wave activity were similar for the two groups. This study demonstrates that the CCK-A receptor might play a role in affecting the level of motor activity, adding hyperphagia, and the circadian rhythm of large movement in these rats prior to the manifestation of NIDDM. In contrast, a CCK-A receptor deficiency does not appear to affect sleep or body temperature in these rats.
(キーワード)
Motor Activity / OLETF / CCK-A / Circadian / Body Temperarure / Slow-wave Activity
Hiroyoshi Sei, Keiko Ikemoto, Ryohachi Arai and Yusuke Morita : Injection of 6-hydroxydopamine into the ventral tegmental area suppresses the increase in arterial pressure during REM sleep in the rat, Sleep Research Online, Vol.2, No.1, 1-6, 1999.
72.
Atsuko Sano, Hiroyoshi Sei, Hiromasa Seno, Yusuke Morita and Hideki Moritoki : Influence of cedar essence on spontaneous activity and sleep of rats and human daytime nap, Japanese Society of Sleep Research, Vol.52, No.2, 133-135, 1998.
(キーワード)
Cedar Essence / Human Daytime Nap / Odor / Spontaneous Activity and Sleep of Rats
73.
Atsuko Sano, Hiroyoshi Sei, Hiromasa Seno, Yusuke Morita and H. Moritoki : Influence of cedar essence on spontaneous activity and human daytime nap., Psychiatry and Clinical Neurosciences, Vol.52, No.2, 133-135, 1998.
(要約)
We investigated whether exposure to the odor of extracted cedar essence (CE) has (i) an influence on spontaneous activity and sleep-wake states of rats and (ii) a sleep-promoting effect on human daytime nap after taking an ordinary night's sleep. In rats exposed to CE, spontaneous activities and amount of wake were significantly decreased, while the amount of non-rapid eye movement (NREM) sleep was significantly increased. In human daytime nap, NREM sleep stage 2 latency was significantly shortened after exposure to CE.
(キーワード)
Animals / Circadian Rhythm / Fourier Analysis / Humans / Male / Odors / Oils, Volatile / Plant Oils / Polysomnography / Rats / Reaction Time / Signal Processing, Computer-Assisted / Sleep Stages / Sleep, REM / Trees / Wakefulness
Mineo Sone, Hiroyoshi Sei, Yusuke Morita, Takeshi Ogura and Saburo Sone : The Effects of Acetazolamide on Arterial Pressure Variability During REM Sleep in the Rat, Physiology & Behavior, Vol.63, No.2, 213-218, 1998.
(キーワード)
Acetazolamide / Arterial pressure / REM sleep / Rat
75.
Hiroo Kawajiri, Na Qiao, Da-Ming Zhuang, Tanihiro Yoshimoto, Hiroshi Hagiya, Shozo Yamamoto, Hiroyoshi Sei and Yusuke Morita : Diurnal Change of Arachidonate 12-Lipoxygenase in Rat Pineal Gland, Biochemical and Biophysical Research Communications, Vol.238, No.1, 229-233, 1997.
76.
Isao Fukunishi, Noriyuki Kawamura, Toshio Ishikawa, Yukihiro Ago, Yasuo Yamasaki, Toshio Fukui, Masayuki Tatemichi, Hiroyoshi Sei, Yusuke Morita, Etsuko Horiguchi and Richard H Rahe : Sleep characteristics of Japanese working men who score alexithymic on the Toronto Alexithymia Scale, Perceptual and Motor Skills, Vol.84, No.3 Pt 1, 859-865, 1997.
77.
Taeko Kiuchi, Hiroyoshi Sei, Hiromasa Seno, Atsuko Sano and Yusuke Morita : Effect of vitamin B12 on the sleep-wake rhythm following an 8-hour advance of the light-dark cycle in the rat, Physiology & Behavior, Vol.61, No.4, 551-554, 1997.
78.
Isao Fukunishi, Noriyuki Kawamura, Toshio Ishikawa, Yukihiro Ago, Hiroyoshi Sei, Yusuke Morita and H Richard Rahe : Mothers' low care in the development of alexithymia: a preliminary study in Japanese college students, Psychological Reports, Vol.80, No.1, 143-146, 1997.
(要約)
We examined the influences of perceived parental bonding on scores on alexithymia in a sample of 232 college students. Ratings on mothers' care, a scale of the Parental Bonding Inventory were significantly and negatively correlated with scores on the Toronto Alexithymia Scale, and also with ratings on Difficulty Describing Feelings but not Difficulty Identifying Feelings and Externally Oriented Thinking. These results were replicated in another sample of 156 college students. Although our findings were based on simple correlations, they suggest that perceived mothers' low care is related to adults' scores on alexithymia, in particular, the construct, Difficulty Describing Feelings.
(キーワード)
Adolescent / Adult / Affective Symptoms / Female / Humans / Male / Mother-Child Relations / Object Attachment / Personality Development / Personality Inventory / Students
Hiroyoshi Sei and Yusuke Morita : Acceleration of EEG theta wave precedes the phasic surge of arterial pressure during REM sleep in the rat, NeuroReport, Vol.7, No.18, 3059-3062, 1996.
(要約)
We investigated temporal relationships among EEG theta frequency, eye movement (EM) burst and phasic surge of arterial pressure (AP) during rapid eye movement (REM) sleep in six rats. Changes in EEG theta frequency, EM number, mean AP (MAP) and heart rate (HR) during 1 s bins were obtained with reference to the onset of the EM bursts. The acceleration of EEG theta frequency preceded both the EM burst and the phasic increases of AP. The increase of MAP was closely correlated with the theta frequency but not the EM number during the period of EM burst. The possible involvement of the limbic system for the generation of phasic surge in AP during REM sleep is discussed.
(キーワード)
EEG theta activity / REM sleep / arterial pressure
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9116240
Hiroyoshi Sei, M Yamamoto and Yusuke Morita : Effect of ambient temperature on power spectral density of arterial pressure during sleep in the rat, Archives Italiennes de Biologie, Vol.134, No.2, 185-190, 1996.
81.
Hiroyoshi Sei and Yusuke Morita : Effect of ambient temperature on arterial pressure variability during sleep in the rat, Journal of sleep research, Vol.5, No.1, 37-41, 1996.
82.
Hiroyoshi Sei, Toshihiro Enai, Hee-Yoon Chang and Yusuke Morita : Heart rate variability during sleep in Down's syndrome, Physiology & Behavior, Vol.58, No.6, 1273-1276, 1995.
(キーワード)
Down's syndrome / Rapid eye movement sleep / Heart rate variability / Frequency analysis
83.
Hiroyoshi Sei, Mineo Sone, Norio Kanamori, Kazuya Sakai and Yusuke Morita : Light-dark difference in arterial pressure variability during REM sleep in the rat., Chronobiology International, Vol.12, No.6, 389-397, 1995.
Norio Kanamori, Kazuya Skai, Hiroyoshi Sei, Antoine Bourvard, Denise Salvert, Giovanna Vanni-Mercier and Michel Jouvet : Effects of decerebration on blood pressure during paradoxical sleep in cats., Brain Research Bulletin, Vol.37, No.5, 545-549, 1995.
Hee-Yoon Chang, Hiroyoshi Sei and Yusuke Morita : Effects of intravenously administered vitamin B12 on sleep in the rat, Physiology & Behavior, Vol.57, No.6, 1019-1024, 1995.
(キーワード)
vitamin B12 / peripheral administration / Sleep-promoting effects / Non-rapid eye movement sleep / Rapid eye movement sleep / Rat
86.
Norio Kanamori, Kazuya Sakai, Hiroyoshi Sei, Denise Salvert, Giovanna Vanni-Mercier, Mitsuaki Yamamoto and Michel Jouvet : Power spectral analysis of blood pressure fluctuations during sleep in normal and decerebrate cats., Archives Italiennes de Biologie, Vol.132, No.2, 105-115, 1994.
Hiroyoshi Sei, Atsuko Sano, Hiromasa Seno and Yusuke Morita : Postoperative changes of rat EEG variance, Physiology & Behavior, Vol.55, No.1, 101-102, 1994.
89.
Hiroyoshi Sei, Taeko Kiuchi, Chang H.Y., Hiromasa Seno and Atsuko Sano : Response of the sleep-wake rhythm to 8-hour advance of the light-dark cycle in the rat, Chronobiol. Int., Vol.11, No.5, 293-300, 1994.
90.
Hiroyoshi Sei, Nario Furuno and Yusuke Morita : Diurnal changes of blood pressure, heart rate and body temperature during sleep in the rat, Journal of sleep research, Vol.6, No.2, 113-119, 1993.
(キーワード)
Blood Pressure / Heart Rate / Body Temperature / Diurnal Rhythm / Sleep Rat
91.
Hiroyoshi Sei, Kazuya Sakai, Mitsuaki Yamamoto and Michel Jouvet : Spectral analyses of PGO-on neurons during paradoxical sleep in freely moving cats, Brain Research, Vol.612, No.1-2, 351-353, 1993.
Hiroyoshi Sei, Taeko Kiuchi, Hee-Yoon Chang and Yusuke Morita : Effects of an eight-hour advance of the light-dark cycle on sleep-wake rhythm in the rat, Neuroscience Letters, Vol.137, No.2, 161-164, 1992.
(キーワード)
phase-advance of the LD cycle / Rapid ryr Movement Sleep / Non-REM Sleep / Rat
94.
Hiroyoshi Sei, Takaharu Azekawa and Yusuke Morita : Ultradian rhythm of 100 min in the dark phase EEG of the rat, Physiology & Behavior, Vol.49, No.1, 207-210, 1991.
Hiroyoshi Sei, Hiromasa Seno and Yusuke Morita : Real-time monitoring of slow-wave sleep by electroencephalogram variance, Chronobiol. Int., Vol.8, No.3, 161-167, 1991.
96.
Takaharu Azekawa, Atsuko Sano, Hiroyoshi Sei and Yusuke Morita : Diurnal changes in pineal extracellular indoles of freely moving rats., Neuroscience Letters, Vol.132, 93-96, 1991.
97.
Takaharu Azekawa, Atsuko Sano, Hiroyoshi Sei, Kazuhiro Aoi and Yusuke Morita : Pineal microdialysis in freely moving rats., Brain Research Bulletin, Vol.26, 413-417, 1991.
98.
Takaharu Azekawa, Atsuko Sano, Kazuhiro Aoi, Hiroyoshi Sei and Yusuke Morita : Concurrent on-line sampling of melatonin in pineal microdialysates from conscious rat and its analysis by high-performance liquid chromatography with electrochemical detection, Journal of Chromatography. B, Biomedical Sciences and Applications, Vol.530, No.1, 47-55, 1990.
(要約)
Dynamic changes of melatonin in microdialysates from the pineal gland of a freely moving rat were repeatedly determined by using on-line high-performance liquid chromatography with electrochemical detection. The detection limit for melatonin, ca. 5 pg, was well below that achieved with other systems. We observed a drastic increase of extracellular pineal melatonin during the transitional phase from the light period to the dark period. This application of microdialysis is a useful tool in the study of the physiological role of the mammalian pineal body.
(キーワード)
Animals / Chromatography, High Pressure Liquid / Circadian Rhythm / 透析 (dialysis) / Male / Melatonin / Microchemistry / Pineal Gland / Quality Control / Rats / Rats, Inbred Strains
Atsuko Sano, Kazuhiro Aoi, Takaharu Azekawa, Hiroyoshi Sei, Hiromasa Seno and Yusuke Morita : Diurnal monoamine variation in young and old rats., --- A microdialysis study ---, Vitamins and Biofactors in Life Science, 577-587, 1992.
The fact that resting wakefulness does not satisfy the need for sleep suggests that sleep has a critical role for the brain, probably for its maintenance or repair. Neuronal oxidative stress, neuroinflammation, or energy insufficiency in the brain is now considered to be a trigger or cause for sleep induction. And the timing for sleep is controlled by circadian clock which also exists in the brain. Sleep is occurred in the brain, which is regulated by the brain itself. "Why do we sleep ?" Although everyone wants to know the answer for this issue, scientists should still question that "How do we sleep"?
Hiroyoshi Sei : Vitamin A and sleep regulation, The Journal of Medical Investigation : JMI, Vol.55, No.1-2, 1-8, Feb. 2008.
(要約)
Vitamin A is the parent compound of retinoids, which regulate gene transcription by binding to nuclear retinoid receptors. Recently, it has been suggested that retinoid signaling pathways are important for adult neural function in health and disease. In this mini review we will summarize the molecular pathway of retinoid and experimental data on this pathway relating to sleep regulation, which suggests that retinoid signaling mechanism may be involved in the homeostatic component of sleep electroencephalogram.
(キーワード)
Animals / Electroencephalography / Homeostasis / Humans / Mice / Receptors, Retinoic Acid / Signal Transduction / Sleep / Vitamin A / Vitamin A Deficiency
Slow wave activity(SWA:<4Hz)in electroencephalograms(EEG)appears during non-REMsleep, which is regulated homeostatically, increasing after wakefulness and returning to baselineduring sleep. Recently, it has been suggested that SWA homeostasis may reflect synaptic changesunderlying a cellular need for sleep. Huber et al.(Nature，430(6995):78‐81，2004)have shownthat SWA homeostasis has a local component, which can be triggered by a learning task involvingspecific brain regions. We also found an impaired SWA rebound after sleep deprivation in fmr1(fragile-X syndrome mental retardation1)knockout mice, indicating an involvement of fmr1genein neural plasticity.Clock genes regulating circadian rhythm are recently thought to modulate several brainfunctions. Spanagel et al.(Nature Medicine，11(1):35‐42，2004)have shown that per2mutantmice show alterations in the glutamatergic system in the brain, accompanied by increasing alcoholintake. They also found that, in humans, genetic variations of human per 2 are related to thealcohol consumption Furthermore, clock genes have been indicated to have important roles in notonly brain but also peripheral organs.In future, we need an animal model for"insomnia"which is one of the most common sleepdisorders in humans.
Circadian rhythm is an endogenous rhythm controlled by a master oscillator (biologicalclock) in the supra-chiasmatic nucleus (SCN), affecting on the almost all physiologicalfunctions including sleep/wake regulation. Recently the biological clock has been shown tofunction at the molecular level, and several circadian-related genes have been identified,such as the Clock, Per 1-3, Bmal 1 or Cry 1, 2.We observed the sleep/wake rhythm in cry 1, 2 double knockout mice and clock mutantmice. Both strains have lost the circadian oscillation in the expression of circadian-relatedgenes. Cry 1, 2 double knockout mice show the entrained sleep/wake rhythm to ordinarylight-dark (LD) cycle, although they show completely flattened rhythm under the constantdark (DD) condition. On the other hand, clock mutant mice show the persistent circadiansleep/wake rhythm under even DD conditions. Although the expression of circadianrelatedgenes do not oscillate, the clock mutant mice have potent circadian rhythm in bodycore temperature, behavior, sleep/wake and cortisol etc. The clock mutant mice have alonger (27 hrs) period of free-running rhythm under DD condition, and the phase of sleep/wake rhythm is delayed for about two hours comparing to the wild-type under LD condition.The important role of the circadian-related genes in the sleep/wake regulation has beenindicated. The functional impairment of the circadian-related genes may be involved in thesleep disorders, such as insomnia or hypersomnia.
Hiroyoshi Sei and Yusuke Morita : Why does arterial blood pressure rise actively during REM sleep?, The Journal of Medical Investigation : JMI, Vol.46, No.1-2, 11-17, Feb. 1999.
(要約)
A large fluctuation in autonomic function is one of the most important characteristics of REM sleep. Arterial blood pressure (AP) increases during the transition from non-REM to REM sleep, showing phasic surges during REM sleep. REM-associated AP changes involve 1) a long-term recovery process after surgery, 2) circadian rhythm, 3) relationships with ambient temperature. REM-associated AP changes are mediated by sympathetic nerves, buffered by baroreflex, abolished in decerebrated cats, and related to hippocampal theta activity in rats. Furthermore, the midbrain dopaminergic system has been recently found to be involved in increases in REM-associated AP.
Sachiko Chikahisa, Kazuhiro Muramatsu, Noriyuki Shimizu, Hiroyoshi Sei and Yuichi Inoue : Sleep-related muscle activity is augmented by administration of serum from RLS patients in Btbd9 mutant mice., International RLS Study Group Meeting, Philadelphia, Aug. 2020.
2.
Junhel Dalanon, Sachiko Chikahisa, Noriyuki Shimizu, Arief Waskitho, Hiroyoshi Sei and Yoshizo Matsuka : Orofacial thermal hyperalgesia in predictable chronic mild stress, Asian Academy of Orofacial Pain and Temporomandibular Disorders, Manila, Oct. 2019.
3.
Junhel Dalanon, Sachiko Chikahisa, S Afroz, Takuma Iwasa, Arief Waskitho, Noriyuki Shimizu, Hiroyoshi Sei and Yoshizo Matsuka : Chronic mild stress exacerbates sleep quality and pain threshold, Philippine Dental Association, Manila, May 2019.
4.
Tetsuya Shiuchi, Takuya Masuda, Noriyuki Shimizu, Sachiko Chikahisa and Hiroyoshi Sei : Role of dopaminergic function in septum on exercise efficiency, FAOSP2019, Mar. 2019.
5.
Sachiko Chikahisa, Tetsuya Shiuchi, Tanioka Daisuke, Noriyuki Shimizu, Otsuka Airi and Hiroyoshi Sei : Chronic mild stress increases aggressive behavior in mice, FAOPS 2019, Kobe, Mar. 2018.
6.
Airi Otsuka, Tetsuya Shiuchi and Hiroyoshi Sei : Intake timing and amounts of high fat diet affect the benefit which improves social avoidance induced by social defeat stress, The 26th Annual Meeting of the IBNS, Jun. 2017.
7.
Sachiko Chikahisa, Harada Saki, Noriyuki Shimizu, Tetsuya Shiuchi, Nishino Seiji and Hiroyoshi Sei : Sleep loss induces diabetes in mice model, Neuroscience 2016, San Diego, USA, Nov. 2016.
8.
Noriyuki Shimizu, Yu Yoshioka, Sachiko Chikahisa, Yuki Kito, Tetsuya Shiuchi and Hiroyoshi Sei : Short time running exercise enhances sleep pressure in mice., Neuroscience 2016, San Diego, USA, Nov. 2016.
9.
Airi Otsuka, Tetsuya Shiuchi, Sachiko Chikahisa and Hiroyoshi Sei : Restricted high fat diet can improve social avoidance induced by social-defeat stress as same as ad libitum high fat feeding, Neuroscience 2016, Nov. 2016.
10.
Airi Otsuka, Tetsuya Shiuchi, Sachiko Chikahisa, Junji Terao and Hiroyoshi Sei : Ingestion of restrickted comfortable food improves social avoidance induced by social defeat stress, 12th Asian Congress of Nutrition, Yokohama, May 2015.
11.
Tetsuya Shiuchi, Airi Otuska, Sachiko Chikahisa, Noriyuki Shimizu and Hiroyoshi Sei : Feeding rhythm during active phase influences hypothalamic regulation of insulin sensitivity in skeletal muscle, 12th Asian Congress of Nutrition, Yokohama, May 2015.
12.
Sachiko Chikahisa, Noriyuki Shimizu, Tetsuya Shiuchi and Hiroyoshi Sei : Contribution of PPARa and Ketone Body to Sleep Homeostasis in Mice, The FASEB journal, Boston, Apr. 2015.
13.
Tetsuya Shiuchi, Airi Otuska, Sachiko Chikahisa, Noriyuki Shimizu and Hiroyoshi Sei : Hypothalamic AgRP-mediated energy metabolism in skeletal muscle is a critical regulatory system in feeding rhythm-induced insulin resistance, Experimental Biology 2015, Boston, Mar. 2015.
14.
Sachiko Chikahisa, Saki Harada, Noriyuki Shimizu, Tetsuya Shiuchi and Hiroyoshi Sei : Sleep quality affects glucose homeostasis in a mouse model, Homeodynamics in Clocks, Sleep and Metabolism, Tokyo Translational Therapeutics Meeting, Sep. 2014.
15.
Sachiko Chikahisa, Noriyuki Shimizu, Tetsuya Shiuchi and Hiroyoshi Sei : Ketone bodies in the brain regulate sleep homeostasis in mice, Gordon Research Conference on Sleep Regulation and Function, Galveston, USA, Mar. 2014.
16.
Sachiko Chikahisa, Noriyuki Shimizu, Tetsuya Shiuchi and Hiroyoshi Sei : Ketone bodies regulate sleep homeostasis, Neuroscience 2013, Nov. 2013.
(要約)
Ketone bodies regulate sleep homeostasis 2013, Nov 9-13, Neuroscience 2013 (San Diego, USA)
17.
Kanna Oura, Tetsuya Shiuchi, Noriyuki Shimizu, Sachiko Chikahisa and Hiroyoshi Sei : Effect of feeding rhythm on sleep/wake regulation, EASD, Sep. 2013.
18.
Tetsuya Shiuchi, Sachiko Chikahisa, Kanna Oura, Noriyuki Shimizu and Hiroyoshi Sei : Different feeding rhythm influences hypothalamic regulation of energy metabolism in skeletal muscle, EASD, Sep. 2013.
19.
Noriyuki Shimizu, Sachiko Chikahisa, Yohei Iwaki, Kazuyoshi Kitaoka and Hiroyoshi Sei : Male adult mice with low birth weight show an increased sleep pressure, Sleep 2012: 26th Annual Meeting of the Associated Professional Sleep Societies, Boston, Jun. 2012.
20.
Sachiko Chikahisa, Tohru Kodama, Yohoei Sagawa, Yuji Ishimaru, Hiroyoshi Sei and Seiji Nishino : Effects of icv administration of a mast cell histamine release enhancer on sleep/wake in wild-type and mast cell deficient mice, Sleep 2012: 26th Annual Meeting of the Associated Professional Sleep Societies, Boston, Jun. 2012.
21.
Sachiko Chikahisa, Noriyuki Shimizu, Hiroaki Fujihara, Tetsuya Shiuchi and Hiroyoshi Sei : Sleep homeostatic regulations in PPAR-knockout mice, Frontiers in Behavioral Brain Science-Solving the mystery of sleep-, Tokyo, Mar. 2012.
22.
Hiroyoshi Sei, Kazuyoshi Kitaoka, Nobuhiro Fujiki, Noriyuki Shimizu, Sachiko Chikahisa, Hiroaki Fujihara, Tetsuya Shiuchi and A Nakai : Mice lacking heat shock factor 1 show evening-type sleep/wake rhythm, World sleep 2011, Kyoto, Oct. 2011.
23.
Noriyuki Shimizu, Sachiko Chikahisa, Yohei Iwaki, Kazuyoshi Kitaoka and Hiroyoshi Sei : Low birth weight by undernutrition during pregnancy elicits anxiety and depression in male offspring mice, World sleep 2011, Kyoto, Oct. 2011.
24.
Sachiko Chikahisa, Noriyuki Shimizu, Kazuyoshi Kitaoka, Yohei Iwaki, Hiroaki Fujihara, Tetsuya Shiuchi and Hiroyoshi Sei : Sleep/wake regulation in PPAR knockout mice, World sleep 2011, Oct. 2011.
25.
Sachiko Chikahisa and Hiroyoshi Sei : PPARs, AMPK and sleep homeostasis, 36th Japanase Society of Sleep Research-World sleep 2011 (Kyoto, Japan), Oct. 2011.
26.
Noriyuki Shimizu, Sachiko Chikahisa, Kazuyoshi Kitaoka and Hiroyoshi Sei : Sleep regulation in PPARalpha knockout mice, Neuroscience 2010, San Diego, USA, Nov. 2010.
27.
Sachiko Chikahisa, Kazuyoshi Kitaoka, Noriyuki Shimizu and Hiroyoshi Sei : Hypothalamic AMPK contributes to homeostatic sleep regulation, Neuroscience 2010, San Diego, USA, Nov. 2010.
28.
Kazuyoshi Kitaoka, Shimizu Mika, Shimizu Noriyuki, Sachiko Chikahisa, Kazuo Yoshizaki and Hiroyoshi Sei : Retinoic acid receptors antagonist LE540 atenuates EEG delta power during sleep via dopamine D1 receptor in mice, Neuroscience 2010, San Diego, Nov. 2010.
29.
Noriyuki Shimizu, Sachiko Chikahisa, Masahiro Oura and Hiroyoshi Sei : Refeeding at light-onset after 24h fasting enhances EEG delta-power in NREM sleep in mice, The 6th Congress of Asian Sleep Research SocietyThe 34th Annual Meeting of Japanese Society of Sleep Research, Osaka, Oct. 2009.
30.
Hiroyoshi Sei, Sachiko Chikahisa and Noriyuki Shimizu : Role of central AMPK in sleep homeostasis, The 6th Congress of Asian Sleep Research SocietyThe 34th Annual Meeting of Japanese Society of Sleep Research, Osaka, Oct. 2009.
31.
Kazuyoshi Kitaoka, Shimizu Mika, Sachiko Chikahisa, Kazuo Yoshizaki and Hiroyoshi Sei : Four-week administration of retinoic acid receptors antagonist LE540 attenuates EEG delta power during sleep in mice, The 6Th Congress of Asian Sleep Research Society, Oct. 2009.
32.
Noriyuki Shimizu, Masahiro Oura, Sachiko Chikahisa and Hiroyoshi Sei : EEG delta power in NREM sleep is enhanced by refeeding after 24-hr fasting in time-dependent manner, 36th International Union of Physiological Sciences, Kyoto, Aug. 2009.
33.
Noriyuki Shimizu, Masahiro Oura, Sachiko Chikahisa and Hiroyoshi Sei : EEG delta power in NREM sleep is enhanced by refeeding after 24-hr fasting in time-dependent manner, 36th International Union of Physiological Sciences, Kyoto, Aug. 2009.
34.
Sachiko Chikahisa, Noriyuki Shimizu, Kazuyoshi Kitaoka, Nobuhiro Fujiki and Hiroyoshi Sei : Central AMPK contributes to sleep regulation, 36th International Union of Physiological Sciences, Kyoto, Aug. 2009.
35.
Kazuyoshi Kitaoka, Atsuko Sano, Sachiko Chikahisa, Kazuo Yoshizaki and Hiroyoshi Sei : Administration of Am80, an agonist of retinoic acid receptor, improves the aging-related decrease of REM sleep in SAMP8 mice, 36th International Congress of Physiological Sciences, Aug. 2009.
36.
Hiroyoshi Sei, Sachiko Chikahisa, Kumiko Tominaga, Tomoko Kawai, Katsutaka Oishi, Norio Ishida and Kazuhito Rokutan : Bezafibrate, a PPARs agonist, enhances EEG delta oscillation during NREM sleep in mice, Neuroscience 2008, Washington DC, USA, Nov. 2008.
37.
Sachiko Chikahisa, Kazuyoshi Kitaoka and Hiroyoshi Sei : Complex auditory stimuli reduce anxiety level in an ovarian steroid hormone-dependent manner in female mice, Neuroscience 2008, Washington DC, USA, Nov. 2008.
38.
Hiroyoshi Sei, Sachiko Chikahisa, Kazuyoshi Kitaoka and Tomoko Kawai : Relationship between spontaneous apnea and surge of arterial pressure during REM sleep in ICR mice, Neuroscience 2007, San Diego, USA, Nov. 2007.
39.
Sachiko Chikahisa, Kazuyoshi Kitaoka, Hiroyoshi Sei, Katsutaka Oishi, Shigenobu Shibata and Norio Ishida : Chronic bezafibrate treatment advances circadian rhythms of sleep and body temperature in mice, 2nd World Congress of Chronobiology, Tokyo, Nov. 2007.
40.
Sachiko Chikahisa, Hiroyoshi Sei, Masaki Morishima, Atsuko Sano, Kazuyoshi Kitaoka, Yutaka Nakaya and Yusuke Morita : Exposure to music in the perinatal period enhances learning performance and alters BDNF/TrkB signaling in mice as adults, Neuroscience 2006, Atlanta, USA, Oct. 2006.
41.
Sachiko Chikahisa, Hiroyoshi Sei, Atsuko Sano, Kazuyoshi Kitaoka and Yusuke Morita : Anxiolytic effects of music depend on ovarian steroid in female mice, International Behavioral Neuroscience Society, Whistler, Canada, May 2006.
42.
Hiroyoshi Sei, N Furuno, M Sakata, K Sano, Norio Kanamori and Yusuke Morita : Diurnal changes of arterial pressure, heart rate and body temperature during sleep in the rat., Abstract of International Congress on Chronobiology, Paris, Sep. 1997.
43.
Atsuko Sano, Hiromasa Seno, Hiroyoshi Sei and Yusuke Morita : An enriched environment increases extracellular acetylcholine levels in the hippocampus of aged rats., The Hippocampus: Functions and Clinical Relevance, 333-338, Amsterdam, 1996.
44.
Norio Kanamori, Hiroyoshi Sei and Kazuo Hosoi : Phase diagram analysis of sleep-wakefulness cycle: triplet subsystems as the reciprocal control factors., Sleep Res., Vol.24A, 2, Nassau, Bahamas, Sep. 1995.
45.
Norio Kanamori, Bouvard A., Hiroyoshi Sei and Sakai K. : Forebrain structures responsible for blood pressure regulation during sleep in cats., 4th International Brain Research Organization World Congress of Neuroscience. : Abstracts, 408, Kyoto, Jul. 1995.
46.
Hiroyoshi Sei, Norio Kanamori, Sakai K., Yamamoto M., Yusuke Morita and Jouvet M. : Role of brain in blood pressure control during paradoxical sleep., Pathophysiology, Vol.1(Suppl):, 379, Kyoto, Nov. 1994.
47.
K. Sakai, Norio Kanamori, Hiroyoshi Sei, G. Vanni-Mercier and D. Salvert : Presumed sympathoexcitatory medullary neurons cease firing during paradoxical sleep., 12th Congress of the European Sleep Research Society; J. Sleep Res., Vol.3, No.Suppl.1, 225, Florence, May 1994.
48.
K. Sakai, Norio Kanamori, Hiroyoshi Sei, M. Yamamoto, D. Salvert and A. Bouvard : Long-term alterations of blood pressure during sleep in normal and decerebrate cats., 12th Congress of the European Sleep Research Society; Sleep Res., Vol.3(Suppl.1), 226, Florence, May 1994.
49.
Atsuko Sano, Kazuhiro Aoi, Takaharu Azekawa, Hiroyoshi Sei, Hiromasa Seno and Yusuke Morita : Diurnal monoamine variation in young and old rats., --- A microdialysis study ---, Symposium 20 Biogenic amine, 577-580, Tokyo, 1992.
国内講演発表:
1.
Sachiko Chikahisa, Dalanon Junhel, Chavan Parimal Ravindra, Tetsuya Shiuchi, Noriyuki Shimizu, Kazuo Okura, Yoshitaka Suzuki, Yoshizo Matsuka and Hiroyoshi Sei : Effects of mild chronic stress on sleep and pain thresholds in mice, 日本生理学会, Mar. 2024.
Noriyuki Shimizu, Sachiko Chikahisa, Tetsuya Shiuchi and Hiroyoshi Sei : Paternal psychological stress exposure prior to mating may cause an impairment of emotional behavior in the next generation via glucocorticoid system, 第46回日本神経科学大会, Aug. 2023.
4.
Noriyuki Shimizu, Sachiko Chikahisa, Tetsuya Shiuchi and Hiroyoshi Sei : Exercise training of paternal mice subjected to continuous psychological stress prior to mating may modify changes in their offsprings emotional behaviors, 日本生理学会 第100回記念大会, Mar. 2023.
5.
Noriyuki Shimizu, Sachiko Chikahisa, Tetsuya Shiuchi and Hiroyoshi Sei : Paternal exposure to psychological stress before mating may influence a formation of emotional behavior in next generation via effect of glucocorticoid, 第45回日本分子生物学会年会, Dec. 2022.
Tetsuya Shiuchi, Keisuke Hashimoto, Ayaka Hashimoto, Airi Otsuka, Sachiko Chikahisa and Hiroyoshi Sei : Dopaminergic neuron activation via gut PPAR-alpha enhanced the motivation for wheel running in mice, NEURO2019, Jul. 2019.
Noriyuki Shimizu, Sachiko Chikahisa, Tetsuya Shiuchi, Airi Otsuka, Daisuke Tanioka and Hiroyoshi Sei : Paternal psychological stress just before mating influences a formation of emotional behavior in next generation offspring mice, The 41st Annual Meeting of the Japan Neuroscience Society, Jul. 2018.
14.
Daisuke Tanioka, Sachiko Chikahisa, Noriyuki Shimizu, Tetsuya Shiuchi, Airi Otsuka and Hiroyoshi Sei : Social behavior is affected by mast cells activity in mice, The 41st Annual Meeting of the Japan Neuroscience Society, Jul. 2018.
15.
増田 拓也, Tetsuya Shiuchi, Sachiko Chikahisa, Noriyuki Shimizu and Hiroyoshi Sei : 中隔核でのドパミン作用と運動効率の関係, 第41回日本神経科学学会大会, Jul. 2018.
16.
大塚 愛理, Tetsuya Shiuchi and Hiroyoshi Sei : 社会敗北性ストレスはβ-アドレナリン受容体を介して血漿中FGF21を増加させる, 第41回日本神経科学学会大会, Jul. 2018.
Noriyuki Shimizu, Sachiko Chikahisa, Tetsuya Shiuchi, Daisuke Tanioka, Airi Otsuka and Hiroyoshi Sei : Paternal psychological stress causes an impairment of emotional behavior in offspring mice, The 95th Annual Meeting of the Physiological Society of Japan, Mar. 2018.
21.
Sachiko Chikahisa and Hiroyoshi Sei : A mouse model of sleep disturbance and their phenotype, 95th Annual Meeting of the Physiological Society of Japan, Mar. 2018.
22.
Daisuke Tanioka, Sachiko Chikahisa, Noriyuki Shimizu, Tetsuya Shiuchi, Airi Otsuka and Hiroyoshi Sei : The role of brain mast cells in mood and behavior, The 95th Annual Meeting of the Physiological Society of Japan, Mar. 2018.
Tetsuya Shiuchi, Noriyuki Shimizu, Airi Otsuka, Sachiko Chikahisa and Hiroyoshi Sei : Alteration of behavior in offspring born from mother lived in the different feeding rhythm during pregnancy, The 94th Annual Meeting of the Physiological Society of Japan, Mar. 2017.
32.
Airi Otsuka, Tetsuya Shiuchi, Sachiko Chikahisa and Hiroyoshi Sei : Restricted high-fat diet is enough to improve social avoidance induced by social-defeat stress, The 39th Annual Meeting of the Japan Neuroscience Society, Jul. 2016.
33.
Noriyuki Shimizu, Yu Yoshioka, Takafumi Misaki, Yuki Kito, Sachiko Chikahisa, Tetsuya Shiuchi and Hiroyoshi Sei : Sleep depth is affected by acute running exercise in mice., The 39th Annual Meeting of the Japan Neuroscience Society, Jul. 2016.
34.
Tetsuya Shiuchi, Noriyuki Shimizu, Airi Otsuka, Sachiko Chikahisa and Hiroyoshi Sei : Behavior alteration on offspring born from mother lived in the different feeding rhythm during pregnancy, The 39th Annual Meeting of the Japan Neuroscience Society, Jul. 2016.
Noriyuki Shimizu, Yu Yoshioka, Takafumi Misaki, Sachiko Chikahisa, Tetsuya Shiuchi and Hiroyoshi Sei : Acute running exercise enhances sleep in mice, The 93rd Annual Meeting of the Physiological Society of Japan, Mar. 2016.
38.
Yuki Kito, Keisuke Hashimoto, Ayaka Hashimoto, Sachiko Chikahisa, Hiroyoshi Sei and Tetsuya Shiuchi : Exercise motivation is enhaced by peripheral PPAR-alpha stimulation, 93rd the Annual Meeting of the Physiological Society of Japan, Mar. 2016.
39.
Airi Otsuka, Kanna Oura, Tetsuya Shiuchi, Sachiko Chikahisa and Hiroyoshi Sei : Relationship between feeding rhythm and sleep pressure, 93rd Annual Meeting of the Physiological Society of Japan, Mar. 2016.
Sachiko Chikahisa and Hiroyoshi Sei : The role of PPARs and ketone body metabolism in the regulation of sleep homeostasis, 92nd Annual Meeting of The Physiological Society of Japan, Mar. 2015.
43.
Airi Otsuka, Tetsuya Shiuchi, Sachiko Chikahisa, Junji Terao and Hiroyoshi Sei : Physical exercise reduces social avoidance induced by defeated stress, 92nd Annual Meeting of The Physiological Society of Japan, Mar. 2015.
44.
Airi Otsuka, Tetsuya Shiuchi, Sachiko Chikahisa, Junji Terao and Hiroyoshi Sei : Effect of restricted high fat diet intake on behavior induced by social defeat stress, The 37th Annual Meeting of the Japan Neuroscience Society, Sep. 2014.
Tetsuya Shiuchi, Akari Futami, Sachiko Chikahisa, Kanna Oura, Hiroaki Fujihara and Hiroyoshi Sei : Effect of feeding rhythm on hypothalamic regulation of energy metabolism, 第90回日本生理学会, Mar. 2013.
Tetsuya Shiuchi, Sachiko Chikahisa, Hiroaki Fujihara, Akari Futami and Hiroyoshi Sei : Effect of differential feeding rhythm on insulin sensitivity and its mechanism, 日本生理学会, Mar. 2012.
58.
Kazuyoshi Kitaoka, Shimizu Noriyuki, Sachiko Chikahisa, Nakagomi Madoka, Shudo Koichi, Hiroyoshi Sei and Kazuo Yoshizaki : Chronic administration of retinoic acid receptor agonist Am80 induces the ADAM10 expression in the hippocampus of SAMP8 mice, The 89th Annual Meeting of the Physiological Society of Japan, Mar. 2012.
原田 慎吾, 小川 眞太郎, 四柳 浩之, 勢井 宏義, 橋爪 正樹 : An LED Lighting Control Circuit to Measure Light Wavelength Dependence on Circadian Rhythm in Mice, 電気関係学会四国支部連合大会講演論文集, 80, 2010年9月.