感情障害の病因に関する神経・免疫・内分泌学的研究

1995 Fiscal Year Annual Research Report

• Project/Area Number: 06304033
• Research Institution: Hiroshima University
• Principal Investigator: 山脇 成人 広島大学, 医学部, 教授 (40230601)
• Co-Investigator(Kenkyū-buntansha): 加藤 進昌 滋賀医科大学, 助教授 (10106213) ; 斉藤 利和 札幌医科大学, 助教授 (50128518) ; 三国 雅彦 群馬大学, 医学部, 助教授 (00125353) ; 樋口 輝彦 昭和大学, 医学部, 教授 (90105883) ; 小山 司 北海道大学, 医学部, 教授 (10113557)
• Keywords: 感情障害 / 免疫 / 内分泌 / 抗うつ薬 / ストレス / セロトニン

Research Abstract

今年度に行われた研究により、以下の事柄が明らかになった。
1.C6培養細胞を用いてセロトニン-2A受容体を介した細胞内カルシウム情報伝達系について検討し、インターロイキン-1前処置によりこの反応が減弱することを明らかにした。また,他の受容体を介した細胞内カルシウム情報伝達系も同様にインターロイキン-1前処置により減弱することが明らかになった。
2.新規抗うつ薬がG蛋白-cAMP生成能を亢進する所見が得られた。
3.有機錫投与により、視床下部-下垂体-副腎皮質機能の変化とともに行動も変化し、うつ病の病態モデルと成り得ることを示した。
4.学習性無カラットの成立にNMDA受容体が重要な役割を担っていることが明らかになった。
5.拘束ストレスによるモノアミン遊離の亢進にインターロイキン-1が関与していることを明らかにした。
6.このようなストレス時における視床下部-下垂体-副腎皮質機能の変化をヒートショック蛋白が調節している可能性が示唆された。
7.抗うつ薬の作用機序として従来から知られているセロトニン再取り込み阻害とノルアドレナリン再取り込み阻害に加えて、ドーパミン再取り込みも阻害されるが,ドーパミン再取り込みはドーパミン・トランスポーターのみならずノルアドレナリン・トランスポーターも介している可能性が示唆された。
8.感情障害および不安障害においてベンゾジアゼピン受容体機能の低下がSPECTを用いた検討により示唆された。以上のように神経・免疫・内分泌学的相互作用から感情障害の病因について検討した。

Research Products

• [Publications] Okamoto, Y.: "Serotonin-induced platelet calcium mobilization is enhanced in mania." Life Sciences. 56. 327-332 (1995)
• [Publications] Okamoto, Y.: "Inhibitory effects of lithium ion on intracellular Ca^<2+> mobilization in the rat hippcampal slices." Neurochemistry International. 26. 233-238 (1995)
• [Publications] Kagaya, A.: "Cyclic GMP generation mediated by 5-HT-2receptors via nitric oxide-dependent pathway and its effects on the desensitization of 5-HT-2receptors inC6 glioma cells." Jorunal of Transmission General Section. 100. 27-38 (1995)
• [Publications] Kagaya, A.: "W-7 facilitates 5-HT_<2A>receptor-mediated intracellular calcium in crease in human platelets." Pharmaceutical Sciences. 1. 141-143 (1995)
• [Publications] 加藤忠史: "双極性障害の遺伝様式について" 脳と精神の医学. 6. 187-192 (1995)
• [Publications] 加賀谷有行: "インターフェロンによるうつ病-その発症機序に関する最近の話題-" Current Insights in Neurological Science. 3. 12-13 (1995)
• [Publications] Kugaya, A.: "Inhibition of serotonin-induced Ca^<2+>mobilization by interleukin-1beta in rat glioma C6BU-1 cells." Brain Research. 682. 151-156 (1995)
• [Publications] Takebayashi, M.: "Effect of acute treatment with sodium valproate on catecholamine and serotonin synthesis in mouse serebral cortex." Neuropsychobiology. 32. 124-127 (1995)
• [Publications] Hayashi, T.: "Modulation by sigma ligands of intracellular Ca^<2+>mobilization by N-methyl-D-aspartate in primary culture of rat frontal cortical neurons." Journal of Phamacology and Experimantal Therapeutics. 275. 207-214 (1995)
• [Publications] Yamawaki, S.: "Pathophysiology of affective disorders: Serotonin receptor function and intracellular calcium sinaling." Serotonin in the Central Nervous System and Periphery. 31-39 (1995)
• [Publications] Ishida, N.: "Audiogenic seizure induces c-fos mRNA expression in the inferior colliculus and not in the hipocampus." Psyschiat. Clin. Neurosci.49. 280-282 (1995)
• [Publications] Sdamatsu, M.: "Altered brain contents of neuropeptides in sponteneously epileptic rats(SER)and tremor rats with absence seizures." Life Sci.57. 523-531 (1995)
• [Publications] Sdamatsu, M.: "The 24-h rhythms in plasma growth hormone, prolactin and thyroid-stimulatng hromone: Effect of sleep deprivation" J. Neuroendocrinol.7. 597-606 (1995)
• [Publications] 西村敏: "新抗てんかん薬とその作用機序" メディコ. 26. 11496-11501 (1995)
• [Publications] Yamada, S.: "Acute immobilization stress reduces (±)DOI-induced5-HT2A receptor-mediated head shakes in rats." Psychophamacology. 119. 9-14 (1995)
• [Publications] Hatta, S.: "Participation of tubulin in the stimulatory regulation of adenylyl cyclase in rat carebral cortex membranes." Journal of Neurochemistry. 64. 1343-1350 (1995)
• [Publications] Watanabe, M.: "Beta adrenergic receptor assay in permeable cells." Biogenic Amine. 11. 235-245 (1995)
• [Publications] Watanabe, M.: "Alterations of the adenylyl cyclase system in mecobalamine-deficient rats." Neuroscience Research Communications. 16. 113-120 (1995)
• [Publications] 井上猛: "SSRIの行動薬理-うつ病と不安神経症に関して-" 神経精神薬理. 17. 229-238 (1995)
• [Publications] 高橋義人: "ラット前頭前野内側部細胞外モノアミン動態に及ぼすMilnacipran(TN-912)急性投与の影響" 基礎と臨床. 29. 27-32 (1995)
• [Publications] Koyama, T.: "Role of serotonin(5-HT)_2receptor function: Implication for the etiology and treatment of depression." Serotonin in the Central Nervous System and Periphery. 121-125 (1995)
• [Publications] 小田垣雄二: "抗うつ薬の薬理学的検証 G蛋白に注目して" 抗うつ薬の科学. 269-285 (1995)
• [Publications] Shintani, F.: "Involvement of interleukin-1 in immobilization stress-induced in crease in plasma adrenocorticotropic hormone and in release of hypothalamic monoamines in the rat." Journal of Neuroscience. 15. 1961-1970 (1995)
• [Publications] Shintani, F.: "Role of interleukin-1 in stress responses: A putative neurotransmitter." Moleculat Neurobiology. 10. 47-71 (1995)
• [Publications] Mikuni, M.: "Rffects of prenatal stressful stimuli on serotonin content in the hypothamamus and pituitary-adrenal response to conditioned fear stress in adult offspring." Serotonin in the Central Nervous System and Periphery.81-87 (1995)
• [Publications] Niitsu, Y.: "Regulation of synapse density of 5-HT-2A receptor agonist and antagonist in the spinal cord of chiken embryo." Neuroscience Letters.195. 159-162 (1995)
• [Publications] Saito, K.: "Serotonin-induced 5-HT-1A rceptor desensitization in C6BU-1 glioma cells transfected with 5-HT-1A receptor gene." Neuroscience Letters. 199. 191-194 (1995)
• [Publications] 大島明彦: "躁状態の薬物療法-最近の動向-" 臨床精神医学. 24. 1301-1308 (1995)
• [Publications] 樋口輝彦: "脳疾患における感情の異常気分障害-躁うつ病" Clinical Neuroscience. 13. 134-138 (1995)
• [Publications] 樋口輝彦: "新しい抗うつ薬" カレントテラピー. 13. 134-138 (1995)
• [Publications] 朝倉幹雄: "抗うつ薬の薬理生化学的作用機序にかかわる問題点" 脳と精神の医学. 6. 245-257 (1995)
• [Publications] Takazawa, A.: "Potent and long-lasting anti-convulsant effects of 1-naphthylactyl spermine, an analogue of Joro spider toxin, against amgdaloid kindled siezures in rats." Brain Research. 706. 173-176 (1996)
• [Publications] 久賀谷亮: "免疫と脳のクロストーク-がん領域におけるPsychopharmacology-" 癌治療と宿主. 8. 31-38 (1996)
• [Publications] 加賀谷有行: "精神障害とカルシウム" Clinical Neuroscience. 14. 217-219 (1996)
• [Publications] Yamaji, T.: "Effects of clomipramine and verapamil on 5-HT-induced intracellular calcium changes in individual C6 rat glioma cells." Neuropsychobiology. (In press). (1996)
• [Publications] 三国雅彦: "躁うつ病の薬理・生化学:セロトニン系" Clinical Neuroscience. (印刷中). (1996)
• [Publications] Yamawaki, S.: "Role of intracellular calcium in the pathophysiology of affective disorders" International Academy for Biomedical and Drug Research. (In press). (1996)
• [Publications] Kagaya, A.: "TJS-010, a new prescription of oriental medicine, enhances 8-OH-DPAT-induced effects in rats." Journal of Neural Transmission General Section. (In press). (1996)
• [Publications] Kagaya, A.: "Effect of citalopram on the desensitization of serotonin-2A receptor-mediated calcium mobilization in rat glioma cells" Progress in Neuropsychophamacology & Biological Psychiatry. (In press). (1996)
• [Publications] Takebayashi, M.: "Gamma-aminobutylic acid in creases intracellular Ca^<2+> concentration in cultured cortical neurons: role of Gl^-transport." European Journal of Pharmacology. (In press). (1996)
• [Publications] Kagaya, A.: "Differential regulation of intracellular signaling systems by sodium fluoride in rat glioma cells." Journal of Neurochemistry. (In press). (1996)
• [Publications] Kato. N.: "Expression of c-fos mRNA after audiogenic siezure in adult rats with neonatal hypothyroidism." Molecul. Brain Res.(In press). (1996)
• [Publications] Ikeda, M.: "Nitric oxide synthase-containing neurons in the hippocampus are preservedin trimethyltin intoxication." Brain Research. (In press). (1996)
• [Publications] Hatta, S.: "Tubulin stimulates adenylyl cyclase acrivity in rat striatal membranes via transfer of guanine nucleotide to Gs portein." Brain Research. (In press). (1996)
• [Publications] Hatta, S.: "Impairment of adenylyl cyclase signal transduction in mecobalamin-deficient rats." European Journal of Pharmacology. (In press). (1996)
• [Publications] Katamura, Y.: "Alterations of tubulin function caused by chronic antidepressant teratment in rat brain." Cell. Mol. Neurobiol.(In press). (1996)
• [Publications] Ozawa, H.: "Cyclic AMP production and degradation systems in postmoretem cortex of depressed patients." Journal Neural Transmission General Section. (In press). (1996)
• [Publications] Hashimoto, S.: "Serotonin reuptake inhibitorsreduce conditioned fear stress-induced freezing behavior in rats." Pharmacol. Biochem. Behav.(In press). (1996)
• [Publications] Inoue, T.: "Serotonergic activation reduces defensife freezing in the conditioned fear paradigm." Pharmacol. Biochem. Behav.(In press). (1996)
• [Publications] Izumi, T.: "Effect of the selective CCK_Breceptor antagonist LY288513 on conditioned fear stress in rats." Europian Journal of Pharmacology. (In press). (1996)
• [Publications] 三国雅彦: "生育環境ストレスによる神経系の発達に伴う可塑的変化-胎生期ストレスを用いたうつ病態モデルの作製をめざして-" 脳と精神の医学. (印刷中). (1996)
• [Publications] 三国雅彦: "精神疾患とドーパミン並びにセロトニン受容体亜型" 臨床精神医学. (印刷中). (1996)
• [Publications] Kato, N.: "The hippocampus, Functions and Clinical Relevance" Kato, N., 480 (1996)