光による生体内情報リズムの制御機構

• Project/Area Number: 08307002
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental physiology (including Physical medicine and Nutritional physiology)
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: 井端 泰彦 京都府立医科大学, 医学部, 教授 (10079684)
• Co-Investigator(Kenkyū-buntansha): 井上 慎一 山口大学, 理学部, 教授 (10274151) ; 岡村 均 神戸大学, 医学部, 教授 (60158813) ; 千原 和夫 神戸大学, 医学部, 教授 (00107955) ; 本間 さと 北海道大学, 医学部, 助教授 (20142713) ; 貴邑 冨久子 横浜市立大学, 医学部, 教授 (40046066)
• Project Period (FY): 1996 – 1997
• Project Status: Completed (Fiscal Year 1997)
• Budget Amount: ¥11,800,000 (Direct Cost: ¥11,800,000); Fiscal Year 1997: ¥5,700,000 (Direct Cost: ¥5,700,000); Fiscal Year 1996: ¥6,100,000 (Direct Cost: ¥6,100,000)
• Keywords: 概日リズム / 視交叉上核 / 遺伝子 / 内分泌 / 行動 / 自律神経 / ゲッ歯類 / ヒト

Research Abstract

本研究は昨年に続き12名の班員による研究により,生体リズム発現及び同調機構,内分泌リズム,自律神経リズム,ヒトにおけるリズム発現,時間記憶などの研究課題について研究を行ってきた。平成9年度に多電極皿上における培養視交叉上核のリズム解析(井端),行動リズム位相変化と哺乳類時間遺伝子(岡村),視交叉上核VIP,AVPニューロンの自律神経反応と高血糖反応への影響(永井),視交叉上核におけるリズム同調機構に対するCREB,CREMの関与(井上)マウスにおける概日リズム突然変異体の分離(海老原),概日リズム光同調に対する心理的ストレスの影響(柴田)GnRHの概日リズム発現に対する視交叉上核AVP,VIPニューロンの影響(貴邑)視床下部成長ホルモン分泌制御機構(千原),条件恐怖刺激に対する視床下部オキシトシン,バソプレシン分泌反応に対する視交叉上核の関与(八木),ヒトにおける生物時間同調因子について(本間),高血圧における血圧の概日リズム機構異常とその治療(田村),睡眠覚醒障害に対する高照度光治療(佐々木)についてそれぞれ研究を行い昨年12月に班会議を開催し研究成果の発表と討論が行われた。特筆すべきことは昨年哺乳動物(ヒトにおいても)にショウジョウバエの時計遺伝子とホモローグである遺伝子が存在することが異なる研究施設から時を同じくして発表されたが(Science,Nature)本研究班の一人である岡村はこの研究グループのひとりであり,彼は続いてこの遺伝子のマウス視交叉上核での発現や光照射による影響や位相変化について"Cell"に発表したことである。即ち哺乳動物における概日リズム発現機序の手がかりが得られたことは大きな成果と考えられる。

Research Products

• [Publications] Kawakami,F.: "Loss of-day-night differences in VIP mRNA levels in the suprachiasmatic nucleus of aged rats" Neurosci.Lett.222. 99-102 (1997)
• [Publications] Tanaka,M.: "Induction of NGFI-A gene expression in the rat suprachiasmatic nucleus by photic stimulation" Brain Res.756. 305-310 (1997)
• [Publications] Tanaka,M.: "Direct retinal projections to GRP neurons to GRP neurons in the suprachiasmatic nucleus of the rat" NeuroReport. 8. 2187-2137 (1997)
• [Publications] Tanaka,M.: "Peptide Expression in GABAergic Neurons in rat suprachiasmatic nucleus in comparison with other forebrain structures : A double labeling insitu hybridization study." The Journal of Histochemistry & Cytochemistry. 45・9. 1231-1237 (1997)
• [Publications] Tamada,Y.: "Neuron-glia interaction in the suprachiasmatic nucleus : A double labeling light and electron" Brain Res.Bull.45・3. 61-67 (1998)
• [Publications] Ibata,Y.: "The suprachiasmatic nucleus : A circadian" The Neuroscientist. 3・4. 215-225 (1997)
• [Publications] Uemura,T.: "Effects of noradrenaline on GnRH-secreting immortalized hypothalamic (GT1-7) neurons." Endocr J. 44. 73-8 (1997)
• [Publications] Funabashi,T.: "Bicuculline infusion advances the timing of Fos expression in LHRH neurons in the preoptic area of proestrous rats." Neuroreport. 8. 771-774 (1997)
• [Publications] Funabashi,T.: "Fos expression by naloxone in LHRH neurons of the mediobasaal hypothalamus pentobarbital sodium in the proestrous rat." J Neuroendocrinol. 9. 87-92 (1997)
• [Publications] Mitsushima,D.: "Possible role of the gamma-aminobutyric acid-A receptor system in the timing of the proestrous luteinizing hormone surge in rats." Endocrinology. 138. 1944-1948 (1997)
• [Publications] Hiruma H: "Neuronal synchronization and ionic mechanisms for propagation of excitation in the functional network of immortalized GT1-7 neurons" J Neuroendocrinol. 9. 835-840 (1997)
• [Publications] Mitsushima,D.: "The maturation of GABA (A) receptor-mediated control of luteinizing hormone secretion in immature male rats." Brain Res. 748. 258-262 (1997)
• [Publications] Yagi,K: "Role of NMDA receptors in the emotional memory associated with neuroendocrine responses to fear stimli in the rat." Neuroscience Research. 30 (in the press). (1998)
• [Publications] Honma,S.: "Circadian rhythms of arginine vasopressin and vasoactive intestinal polypeptide do not depend on cytoarchitecture of dispersed celI culture of rat suprachiasmatic nucleus." Neuroscience. (印刷中). (1998)
• [Publications] Shinohara,K.: "Circadian release of amino acids in the suprachiasmatic nucleus in vitro." Neuroreport. 9(印刷中). (1998)
• [Publications] Yoshihara,T.: "Independence of feeding-associated circadian rhythm from light conditions and meal intervals in SCN lesioned rats." Neurosci.Lett.222. 95-98 (1997)
• [Publications] Nakamura,K.: "Daily melatonin intake resets circadian rhythms of a sighted man with no-24-hour sleep-wake syndrome who lacks nocturnal meltaonin rise." Psychiat.Clin.Neurosci.51. 121-127 (1997)
• [Publications] Nakamura,K.: "A sighted man with non-24-hour sleep-wake syndrome showed damped plasma melatonin rhythm." Psychiat.Clin.Neurosci.51. 115-119 (1997)
• [Publications] Hashimoto,S.: "Free-running circadian rhythm of melatonin in a sighted young man despite a 24-hr sleep pattern : a non-24-hour circadian syndrome." Psychiat.Clin.Neurosci.51. 109-114 (1997)
• [Publications] Mitsuaki Okutani: "What Time Is the "Biologic Zero Hour of Circadian Variability"" American Journal of Hypertension. vol.10 no.7. 756-762 (1997)
• [Publications] Yasuaki Mochizuki: "Limited Reproducibility of Circadian Variation in Blood Pressure Dippers and Nondippers." American Journal of Hypertension. vol.11 (未定). (1998)
• [Publications] 高橋 敏治・佐々木三男: "現代人の睡眠行動パターンの問題点とその対策" 睡眠と環境. (印刷中).
• [Publications] 高橋 敏治: "海外渡航者の悩み「時差ぼけ症候群」の原因に迫る" Travel Management. 21・3. 12-18 (1998)
• [Publications] 高橋 敏治: "生体リズムとうつ病" 治療学. 31・6. 71 (1997)
• [Publications] Shigeyoshi,Y.: "Light-induced resetting of a mammalian circadian clocks associated with rapid naanction of the mperl transcript" Cell. 91. 1043-1053 (1997)
• [Publications] Tei,H.: "Circadian oscillation of a mammalian homolog of the Drosophila period gene" Nature. 389. 512-516 (1997)
• [Publications] Ban,Y.: "Development of circadian VIP rhythm in the rat suprachiasmatic nucleus" J.Neurosci.17. 3920-3931 (1997)
• [Publications] Shigeyosshi,Y.: "Coexistence of preprosonatostatin and preprotachykenin A menA in neurons of the rat SCN" Mol.Brain Res.48. 159-163 (1997)
• [Publications] Ibata,Y.: "The suprachiasmatic nucleus : a circadian oscillator" Neuroscientist. 3. 215-215 (1997)
• [Publications] Takumi,T.: "A new mammalian period gene predominantly expressed in the SCN" Genes Cells. (In press). (1998)
• [Publications] T.Shima,et al.: "Melatonin suppresses hyperglycemia caused by intracerebroventricular injection of 2-deoxyD-glucose in rats." Neuroscience Letters. 226. 119-122 (1997)
• [Publications] K.Sugahara,et al.: "Little or no response to 24-h water deprivation of fos-like immunoreactivity in vasopressinergic magnocellular neurons in the hypotitalamus of hereditary microphthaimic rats." Experimental Animals. 46. 141-145 (1997)
• [Publications] A.Tokunaga,et al.: "Imunohistochemical characterization of the suprachiasmatic nucleus and the intergeniculate leaflet in the hereditary microphthalmic rats." Neuroscience Research. 27. 57-63 (1997)
• [Publications] C.Fukuhara et al.: "Day-night variation of petuitary adenylate cyclase-activating polypeptide leuel in the rat suprachiasmatic nucleus" Neurosci Letters. 229. 49-52 (1997)
• [Publications] C.Fukuhara et al.: "Circadian rhythms of vasoaetive intestival polypeptide sentent in the vat SCN under free-running conditions" Neurosci.Lett.(in Press).
• [Publications] 井上 愼一、原田由美子: "視交叉上核におけるニューロペプチド発現" ブレインサイエンス. 18. 33-39 (1997)
• [Publications] 井上 愼一: "サーカディアンリズム" ヒューマンサイエンス. 8. 14-17 (1997)
• [Publications] 井上 愼一: "視交叉上核における神経伝達物質" 生体リズムと精神疾患. 15. 175-191 (1997)
• [Publications] Yamanouchi,S.: "Decreased level of light-induced Fos expression in the suprachiasmatie nucleus of diabetic rats." Neuroscience Letters. 227. 103-106 (1997)
• [Publications] T.Yoshimura: "Spectral sensitivity of photoreceptors mediating phase-shifts…" Journal of Comparative physiology A. 178. 797-802 (1996)
• [Publications] S.Ebihara: "In vivo microdialysis studies of pineal and ocular melatonin…" Biological Signals. 6. 233-240 (1997)
• [Publications] T.Yoshimura: "Genetic mapping of the rat serotonin N-Acetyltransferase…" Cytogenet Cell Genet. (in press).
• [Publications] T.Yoshimura: "Decline of circadian photosensitivity associated with…" Brain Research. (in press).
• [Publications] A.Adachi: "Phase-relationship and mutual effects between circadian…" Brain Research. (in press).
• [Publications] 石川 明: "QTL解析:基礎理論と行動遺伝学への応用" 比較生理生化学. (印刷中).
• [Publications] Kaji.H, Okimura.Y, Abe.H, Chihara.K: "Novel compound heterozygous mutations of growth hormone (GH) receptor gene in a patient with GH insensitivity syndrome" J Clin Endocrinol Metab. 82. 3705-3709 (1997)
• [Publications] Takahashi.Y, Okimura.Y, Abe.H, Chihara.K: "Leptin induces mitogen-activated protein kinase-dependent proliferation of C3H10T1/2 cells." J Biol Chem. 272. 12897-12900 (1997)
• [Publications] Takahashi.Y, Kaji.H, Okimura.Y, Chihara.K: "Biologically inactive growth hormone caused by an amino acid substitution." J Clin Invest.100. 1159-1165 (1997)
• [Publications] Wada.S, Kaji.H, Yoshimura.K, Chihara.K: "Characterization of GH3 cells overexpressing basic fibroblast growth factor (FGF-2)." J Neuroendocrinol. 9. 423-430 (1997)
• [Publications] Matsuoka.H, Iwata.N, Chihara.K, Matsui.T: "Expression of a kinase-detective Eph-like receptor in the normal human brain." Biochem Biophys Res Commun. 235. 487-492 (1997)
• [Publications] Okuda.S, Kanda.F, Kawahara.Y, Chihara.K: "Regulation of inducible nitric oxide synthase expression in L6 rat skeletal muscle cells." Am J Physiol. 272. C35-40 (1997)
• [Publications] Honma,K.: "Excerpta Medica International Congress Series" Non-SCN rhythm in the circadian domain. (印刷中), (1998)
• [Publications] Honma,K.: "Sleep and Sleep Disorders-from Molecule to Behavior,O.Hayaishi and S.Inoue (eds.),Academic Press" Sleep and melatonin rhythm in humans., 223-236 (1997)
• [Publications] Tanaka, M.: "Somatostatin neurons form a distinct peptidergic neuronal group in the rat suprachiasmatic nucleus : a double labeling in situ hybrldization study" Neurosci Lett.215. 119-122 (1996)
• [Publications] Kawakami, F.: "Effect of serotonergic inpts to VIPmRNA in the rat suprachiasmatic nucleus" Int. Acad. Biomed. Drug. Res.11. 161-167 (1996)
• [Publications] Tanaka, M.: "The origin of catecholaminergic innervation in the rostral ventromedial medulla oblongata of the rat" Nerosci. Lett.207. 53-56 (1996)
• [Publications] Tanaka, M.: "Induction of NGFI-A gene expression in the rat suprachiasmatic nucleus photic stimulation" Brain Res.(in press). (1997)
• [Publications] Ibata, Y.: "The suprachiasmatic nucleus : Acircadian oscillator" The Neuroscientist. (in press). (1997)
• [Publications] 井端泰彦: "生体リズムの発現及び同調機構" BME. 10, 8. 12-21 (1996)
• [Publications] Toshiya Funabashi: "Fos expression by naloxone in LHRH neurons of the mediobasal hypcthalamus and effects of pentobarbital sodivin in the proestrous rat" Jourual of Neuroendocrinology. Vol. 9. 87-92 (1997)
• [Publications] Toshiya Funabashi: "Bicuculline infusion advancs the timing of Fos expression in LHRH neurens in the preoptic area of proestrous rats" Nevro Report. Vol. 8 (in press). (1997)
• [Publications] Dai Mitsushima: "Possible role of the γ-amincbutyric acid-A receptor system in the timing of the proestrous lutenizing hormone surge in rats" Endocrinology. (in press). (1997)
• [Publications] Kinji Yagi: "A benzodiazepine, chlordiazepoxide, blocks vasopressin and oxytocin release after footshocks but not osmotic stimulus in the rat." Neuroscience Letters. 203. 49-52 (1996)
• [Publications] Kinji Yagi: "Chlordiazepoxide discriminates between the neural circuits mediating neuroendocrine responses to fear-and anxiety-producing stimli in the rat." Neuroscience Research. 24. 151-158 (1996)
• [Publications] Tatsshi Onaka: "Norepinephrine depletion impairs neuroendocrine responses to fear but not novel environmental stimuli in the rat." Brain Research. 713. 261-268 (1996)
• [Publications] Tatsushi Onaka: "A selective role of brainstem noradrenrgic neurons in oxytocin release from the neurohypophysis following noxious stimuli in the rat." Neuroscience Research. 25. 67-75 (1996)
• [Publications] Kinji Yagi: "An NMDA-receptor antagonist, MK-801 blocks the supressive vasopressin response to fear-but not to anxiety-related stimuli in the rat." Neuroscience Research. 20 (Supplement). S253- (1996)
• [Publications] Tatsushi Onaka: "Effects of noradrenaline depletion in the bed uncleus of the stria terminalis on neuroendocrine responses to fear-related stimuli in the rat." Neuroscience Research. 20 (Supplement). S254- (1996)
• [Publications] Hashimoto, S.: "Midday exposure to bright light changes the circadian organization of plasma melatonin rhythm in humans." Neurosci. Lett.(印刷中). (1997)
• [Publications] Hashimoto, S.: "Free-running circadian rhythm of melatonin in a sighted young man despite a 24-hr sleep pattern : a non-24-hour circadian syndrome." Psychiat. Clin. Nerosci.(印刷中). (1997)
• [Publications] Nakamura, K.: "A sighted man with non-24-hour sleep-wake syndrome showed damped plasma melatonin rhythm." Psychiat. Clin. Nerosci.(印刷中). (1997)
• [Publications] Nakamura, K.: "Daily melatonin intake resets circadian rhythms of a sighted man with no-24-hour sleep-wake syndrome who lacks nocturnal melatonin rise." Psychiat. Chin. Nerosci.(印刷中). (1997)
• [Publications] Honma, K.: "Sleep and melatonin rhythm in humans." Sleep and Sleep Disorders-from Molecule to Behavior. (印刷中). (1997)
• [Publications] Hashimoto, S.: "Vitamin B12 enhances the phase-response of circadian melationin rhythm to a single bright light exposure in humans." Neruscience Letters. 220. 129-132 (1996)
• [Publications] Hashimoto, S.: "Melatonin rhythm is not shifited by lights which suppress noctural melatonin in humans under entrainment." American Journal of Physiology. 270. R1073-R1077 (1996)
• [Publications] Abe. H.: "Substance P receptor regulates the photic induction of Fos-like prontein in the suprachiasmatic nucleus of Syrian hamsters." Brain Research. 708. 135-142 (1996)
• [Publications] Yoshihara, T.: "Methamphetamine stimulates the release of neuropeptide Y and noradrenaline from the paraventricular nucleus in rats." Brain Research. 707. 119-121 (1996)
• [Publications] Y. Takahashi, H. Kaji, Y. Okimura, K. Goji, H. Abe K. Chihara: "Brief Report : Short stature caused by a mutant growth hormone" The New England Journal of Medicine.334. 432-436 (1996)
• [Publications] H. Yagi, H. Kaji, M. Sato, Y. Okimura, K. Chihara: "Effect of intravenours or intracerebroventricular injections of His-D-Trp-Ala-Trp-D-Phe-Lys-NH_2 on GH release in conscios, freely moving male ra" Neuroendocrinology. 63. 198-206 (1996)
• [Publications] M. Mitani, H. Kaji. H. Abe, K. Chihara: "Growth hormone (GH) -releasing peptide and GH releasing hormone stimulate GH release from subpopulations of somatotrophs in rats" Journal of Neroendocrinology. 8. 825-830 (1996)
• [Publications] Y. Xu, H. Kaji, Y. Okimura, T. Matsui, H. Abe, K. Chihara: "Paracrine stimulation of cell growth by cholecystokinin/gastrin through cholecystokinin-B receptor on GH_3 cells in vitro" Neuroendocrinology. 64. 280-285 (1996)
• [Publications] M. Tanaka, H. Okamura, T. Matsuda, Y. Shigeyoshi, Y. Hisa, K. Chihara: "Somatostatin neurons form a distinct peptidergic neuronal group in the rat suprachiasmatic nucleus : a double in situ hybridization study" Neroscience letters. 215. 119-122 (1996)
• [Publications] A. Nagata, M. Ito, N. Iwata, J. Kuno, H. Takano, O. Minowa, K. Chihara, T. Matsui, T. Noda.: "G protein-coupled cholecystokinin-B/gastrin receptors are responsible for physilogical cell growth of the stomach mucosa in vivo" Proc. Natl. Acad. Sci. USA. 93. 11825-11830 (1996)
• [Publications] Ijiri H, Iwasaki H, Mochizuki Y, et al.: "Circadian Blood Pressre Profile and Left Ventricular Hypertrophy in Essential Hypertension." Ther. Res.17 (8). 99-104 (1996)
• [Publications] Umetani K, Tamura K, Komori, etal.: "Inhibitoly Effect of CV4151, a Thromboxane A2 Synthetase Inhibitor, on Ventricular Arrhythmias Induced by Coronary" Jpn. Cir. J.60 (6). 349-354 (1996)
• [Publications] Mochizuki Y, Okutani M, Iwasaki H. et al.: "Reproducibility of Nocturnal Blood Pressure Reduction Rate and the Prevalence of 'Non-Dippers' Using 48-Hour Ambulatory Blood Pressnre Mohitring in Patients with Essential Hypertension." Annals of The New York Academy of Sciences. 783. 330-332 (1996)
• [Publications] 望月 淳 他9名: "健常者における夜間安静期血圧および昼間活動期血圧変動に及ぼす加令の影響。" 脈管学. 36 (6). 311-325 (1996)
• [Publications] 田村康二 他2名: "冠インターベンション療法と心不全" 日本成人病学会雑誌. 22. 40- (1996)
• [Publications] Okamura H, Sugano T, Ibata Y: "Reserpine-induced immnocytochemical change of neuropeptide Y in the hypothalamic arcuate nucleus" Neurochem. Res.21. 239-243 (1996)
• [Publications] Nakagawa T, UkaiK, OhyamaT Koida M, Okamura H: "Effects of the synthesized growth hormone releasing peptide, KP-102, on growth hormone release in sodium glutamate monohydrate-treated low growth rats" Life Sci.59. 705-712 (1996)
• [Publications] Uno T, Hisa Y, Tadaki N, Okamura H, Ibata Y: "Tyrosine hydroxylase immnoreactive cells in the nodose ganglion for the canine larynx" NeuroReport. 7. 1373-1376 (1996)
• [Publications] Umehara K, Kataoka, OguraT Esumi H, Ibata Y, Okamura H: "Comparative distribtion of nitric oxide synthase (NOS) in pancreas of the dog and rat" Brain Res. Bull.(In press).
• [Publications] Yokoyama C, Okamura H: "Self-injurious behavior and dopaminergic neuron system in neonatal 6-OHDA lesioned rat. 1 Dopaminergic neurons and receptors" J. Pharmacol. Exp. Ther.(In press).
• [Publications] Okamura H. Murakami T, Yokoyama, Nakamura, Ibata Y: "Self-injurious behavior and dopaminergic neuron system in neonatal 6-OHDA lesioned rat : Intracerebral microinjection of dopamine agonists and antagonists." J. Pharmacol. Exp. Ther.(In press).
• [Publications] Kimiko Shimizu: "An immunotoxin, anti-VIP antibody-ricin A chain conjugate eliminates neurons in the hypothalamic suprachiasmatic nucleus seletively and abolishes the circadian rhth of water intake." Brain Research Bulletin. 41 (6). 369-378 (1996)
• [Publications] Katsuya Nagai: "Bilateral lesions of the hypothalamic suprachiasmatic nucleus eliminated sympathetic response to intracranial injection of 2-treoxy-D-glucose and VIP resculd this respons" Brain Research Bulletin. 39 (5). 293-297 (1996)
• [Publications] Katsuya Nagai: "SCN output derives the autonomic nervous system : with special reference to the autonomic function related to the regulation of giucose metabolism" Progress in Brain Research. 111. 253-272 (1996)
• [Publications] S. I. T. Inouye: "Circadian phythms of neuscpeptidesin the Suprachisontic nuclecs" Progress in Brain Reseerch. 111. 75-90 (1996)
• [Publications] Nishikawa, Y.: "Methylcopolamine imduces a long-lasting enhece ment of the field potontal in rat sprachiassati mucleus slies" Neuroscine Letters. 220. 199-202 (1996)
• [Publications] Hisa Y, Uno T, Tadaki N, Koike, Okamra H, Ibata Y: "Nitric oxide participation in laryngeal innervation Vocal Fold Physiology (Davis PJ and Fletcher NF eds)" Singular Publishing Group (Sandiego), 433 (1996)