1993 年度実績報告書

脳内神経伝達物質の長期効果に関する分子生物学的研究

研究課題

研究課題/領域番号	04044143
研究機関	放送大学
研究代表者	鬼頭昭三放送大学, 教養学部, 教授 (00010140)
研究分担者	仙波純一放送大学, 教養学部, 助教授 (30183429) BARNARD Elic Royal Free Hospital School of Medicine, Professor VENTER Graig National Institute of Health, Chief Prof JOH Tong H Cornell University Medical College, Professor 三好理絵東京女子医科大学, 助手 (80209965) 遠山正彌大阪大学, 医学部, 教授 (40028593) 佐藤公道京都大学, 薬学部, 教授 (80025709) OLSEN Richar UCLA School of Medicine, Professor
キーワード	steroid hormon / dexamethasone / in vivo microdialysis / estrogen / glutamate / 海馬 / Ca^<2+> / 扁桃核
研究概要	ステロイドホルモンは、核内または、細胞質内の受容体を介して、genomicな長期効果を持つ他に、近年は、細胞膜の特異的結合部位を介して、non-genomicな短期効果を持つことが知られている。長期効果と短期効果のクロストークを明らかにすることが本研究の目的である。一方、ステロイドホルモンは神経細胞に対し毒性を示す可能性が私達によって明らかされ、そのメカニズムを探ることによって上記の研究目的を達することにしている。すなわち、dexamethasoneは海馬培養神経細胞にたいするカイニン酸の毒性を用量依存的に増強する。一方、dexamethasoneは単独では毒性を示さない。このメカニズムを探る目的でin vivo microdialysisによって、ラット海馬における神経伝達物質の放出に対するdexamethasoneの影響を観察した。その結果dexamethasoneはラット海馬からのglutamateの放出を増強することを認めた。genomicな作用としては海馬の神経細胞が傷害されたときに修複機転として働くHGF遺伝子の発現をdexamethasoneが抑制することが考えられたが、この点について確認の実験を継続中である。更に、estrogenが扁桃核培養神経細胞に対して、単独で高濃度で障害作用を示すことがみられた。このメカニズムを探るために扁桃核にestrogenを加えることにより細胞内Ca^<2+>imagingの実験を行った。その結果10分間、もしくはそれ以上にわたってCa^<2+>濃度の上昇をきたすことを認めた。Ca^<2+>濃度の上昇は短い潜時で急激な立ち上がりを示す場合と、徐々に上昇する場合とが見られた。これらのメカニズムについてさらに検討を続けている。

研究成果
(31件)

すべてその他

すべて文献書誌 (31件)

[文献書誌] Miyoshi,R.: "Effect of caerulein on expression of the immediate-early genes c-fos and zif/268 in the rat brain." Neuroscience Letters. 145. 205-208 (1992)
[文献書誌] Miyoshi,R.: "Effect of estrogen on immediate early gene exprssion in the rat brain." Society for Neuroscience Abstracts. 18. 57.1 (1992)
[文献書誌] Kito,S.: "Effect of glucocorticoid on in vivo release of neurotransmitters from the rat hippocampus." Society for Neuroscience Abstracts. 18. 57.4 (1992)
[文献書誌] Shimoyama,M.: "Effect of mineralcorticoid on in vivo release of neurotransmitters from the rat hippocampus." Society for Neuroscience Abstracts. 18. 57.3 (1992)
[文献書誌] Kito,S.: "A cytoprotective effect of nicotine on hippocampal neurons." Society for Neuroscience Abstracts. 19. 772.15 (1993)
[文献書誌] Miyoshi,R.: "Effect of nicotine on neurotransmitter release from the rat hippocampus." Society for Neuroscience Abstracts. 19. 384.6 (1993)
[文献書誌] Kito,S.: "Effect of glucocorticoid on hippocampal neurons:in vivo and in vitro studies." Neurochemical Research. 18. 801-860 (1993)
[文献書誌] Kokka,N.: "The kindling model of alcohol dependence:similar persistent reduction in seizure threshold to pentylenetetrazol in animals receiving chronic ethanol" Alcohol clin.Exp.Res.17. 525-531 (1993)
[文献書誌] Kokka,N.: "The kindling model of alcohol dependence:similar persistent reduction in seizure threshold to pentylenetetrazol in animals receiving chronic ethanol" Alcohol clin.Exp.Res.17. 525-531 (1993)"or chronic pentylenetrazol"
[文献書誌] Longoni,B.: "Enhancement of gamma-aminobutyric acidA receptor function and binding by the volatile anesthetic halothane" J.Pharmacol.Exp.Ther.266. 153-159 (1993)
[文献書誌] Browning,M.D.: "Phosphorylation of the GABAA receptor by CAMP-dependent protein kinase and by protein kinase C:analysis of the substrate domain" Neurochem.Res.18. 95-100 (1993)
[文献書誌] Maeda,T.: "Bidirectional modulation of long-term potentiation by carbachol via M_1 and M_2 muscarinic receptors in guinea pig hippocampal mossy liber‐CA3 synapses." Brain Research Biophysical Research Communications. 619. 324-330 (1993)
[文献書誌] Ozaki,M.: "A vaccinia virus vector for efficiently introducing into hippocampal slices." Biochemical and. 193. 653-660 (1993)
[文献書誌] Nakamura,S.: "Potentiation of a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid(AMPA)-selective glutamate receptor function by a nootropic drug.idebenone." Biol.Pharm.Bull.17. 70-73 (1994)
[文献書誌] Masana Y: "Localization of trkB mRNA in postnatal brain development." J Neurosci Res. 35. 468-79 (1993)
[文献書誌] Yoshimura R: "Localization of oxytocin receptor messenger ribonucleic acid in the rat brain." Endocrinology. 133. 1239-46 (1993)
[文献書誌] Takatsuji K: "Differential effects on substance P immunoreactivity in rat suprachiasmatic and olivary pretectal nuclei." Neuroreport. 4. 647-50 (1993)
[文献書誌] Kito,S.: "A cytoprotective effect of nicotine on hippocampal neurons." Society for Neuroscience Abstracts. 19. 772.15 (1993)
[文献書誌] Miyoshi,R.: "Effect of nicotine on neurotransmitter release from the rat hippocampus." Society for Neuroscience Abstracts. 19. 384.6 (1993)
[文献書誌] Kito,S.: "Effect of glucocorticoid on hippocampal neurons:in vivo and in vitro studies." Neurochemical Research. 18. 801-860 (1993)
[文献書誌] Weiser,M.: "Differntial spatial and temporal gene expression in response to axotomy and differentation following transection of the medial forebrain bundle" J.Neurosci.13. 3472-3484 (1993)
[文献書誌] Kim,K.S.: "Both the basal and inducible transcription of the tyrosine hydroxylase gene are dependent upon a cAMP response element" J.Biol.Chem.268. 15689-15695 (1993)
[文献書誌] Weiser,M.: "Axotomy-induced differential gene induction in neurons of the locus ceruleus and substantia nigra." Brain Res.Mol.Brain Res.17. 319-327 (1993)
[文献書誌] Fraser,C.M.: "Beta-adrenergic and muscarinic cholinergic receptors:relationship between primary structure,receptor function and regulation" American Review of Respiratory Disease. 141. (1990)
[文献書誌] Venter,J.C.: "Isolation,purification and molecular biology of cell membrane receptors" Comprehensive Medicinal Chemistry. 3. (1990)
[文献書誌] Venter,J.C.: "Genome sequencing conference I:Summary" Genomics. 8. (1990)
[文献書誌] Usherwood,P.N.: "Channels formed:by M2 peptides of a putative glutamate receptor subunit of locust." EXS. 63. 241-249 (1993)
[文献書誌] Kerry,C.J.: "Reconstitution of glutamate receptor proteins purified from xenopus central nervous system into artificial bilayers." Mol.Pharmacol.44. 142-152 (1993)
[文献書誌] Webb,T.E.: "Cloning and functional expression of a brain G-proteincoupled ATP receptor." FEBS Lett.324. 219-225 (1993)
[文献書誌] Semba,J.: "Antiepileptic drug phrmacokinetics and neuropharmacokinetics in individual rats by repetitive withdrawal of blood and cerebrospinal fluid:milacemide." Br.J.Pharmacol.108. 1117-1124 (1993)
[文献書誌] Semba,J.: "Milacemide effcts on the temporal interrelationship of amino acids and monoamine metabolites in rat cerebrospinal fluid." European Journal of Pharmacology. 230. 321-326 (1993)

1993 年度 実績報告書

脳内神経伝達物質の長期効果に関する分子生物学的研究

研究代表者

鬼頭 昭三 放送大学, 教養学部, 教授 (00010140)

研究成果

[文献書誌] Miyoshi,R.: "Effect of caerulein on expression of the immediate-early genes c-fos and zif/268 in the rat brain." Neuroscience Letters. 145. 205-208 (1992)

[文献書誌] Miyoshi,R.: "Effect of estrogen on immediate early gene exprssion in the rat brain." Society for Neuroscience Abstracts. 18. 57.1 (1992)

[文献書誌] Kito,S.: "Effect of glucocorticoid on in vivo release of neurotransmitters from the rat hippocampus." Society for Neuroscience Abstracts. 18. 57.4 (1992)

[文献書誌] Shimoyama,M.: "Effect of mineralcorticoid on in vivo release of neurotransmitters from the rat hippocampus." Society for Neuroscience Abstracts. 18. 57.3 (1992)

[文献書誌] Kito,S.: "A cytoprotective effect of nicotine on hippocampal neurons." Society for Neuroscience Abstracts. 19. 772.15 (1993)

[文献書誌] Miyoshi,R.: "Effect of nicotine on neurotransmitter release from the rat hippocampus." Society for Neuroscience Abstracts. 19. 384.6 (1993)

[文献書誌] Kito,S.: "Effect of glucocorticoid on hippocampal neurons:in vivo and in vitro studies." Neurochemical Research. 18. 801-860 (1993)

[文献書誌] Kokka,N.: "The kindling model of alcohol dependence:similar persistent reduction in seizure threshold to pentylenetetrazol in animals receiving chronic ethanol" Alcohol clin.Exp.Res.17. 525-531 (1993)

[文献書誌] Kokka,N.: "The kindling model of alcohol dependence:similar persistent reduction in seizure threshold to pentylenetetrazol in animals receiving chronic ethanol" Alcohol clin.Exp.Res.17. 525-531 (1993)"or chronic pentylenetrazol"

[文献書誌] Longoni,B.: "Enhancement of gamma-aminobutyric acidA receptor function and binding by the volatile anesthetic halothane" J.Pharmacol.Exp.Ther.266. 153-159 (1993)

[文献書誌] Browning,M.D.: "Phosphorylation of the GABAA receptor by CAMP-dependent protein kinase and by protein kinase C:analysis of the substrate domain" Neurochem.Res.18. 95-100 (1993)

[文献書誌] Maeda,T.: "Bidirectional modulation of long-term potentiation by carbachol via M_1 and M_2 muscarinic receptors in guinea pig hippocampal mossy liber‐CA3 synapses." Brain Research Biophysical Research Communications. 619. 324-330 (1993)

[文献書誌] Ozaki,M.: "A vaccinia virus vector for efficiently introducing into hippocampal slices." Biochemical and. 193. 653-660 (1993)

[文献書誌] Nakamura,S.: "Potentiation of a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid(AMPA)-selective glutamate receptor function by a nootropic drug.idebenone." Biol.Pharm.Bull.17. 70-73 (1994)

[文献書誌] Masana Y: "Localization of trkB mRNA in postnatal brain development." J Neurosci Res. 35. 468-79 (1993)

[文献書誌] Yoshimura R: "Localization of oxytocin receptor messenger ribonucleic acid in the rat brain." Endocrinology. 133. 1239-46 (1993)

[文献書誌] Takatsuji K: "Differential effects on substance P immunoreactivity in rat suprachiasmatic and olivary pretectal nuclei." Neuroreport. 4. 647-50 (1993)

[文献書誌] Kito,S.: "A cytoprotective effect of nicotine on hippocampal neurons." Society for Neuroscience Abstracts. 19. 772.15 (1993)

[文献書誌] Miyoshi,R.: "Effect of nicotine on neurotransmitter release from the rat hippocampus." Society for Neuroscience Abstracts. 19. 384.6 (1993)

[文献書誌] Kito,S.: "Effect of glucocorticoid on hippocampal neurons:in vivo and in vitro studies." Neurochemical Research. 18. 801-860 (1993)

[文献書誌] Weiser,M.: "Differntial spatial and temporal gene expression in response to axotomy and differentation following transection of the medial forebrain bundle" J.Neurosci.13. 3472-3484 (1993)

[文献書誌] Kim,K.S.: "Both the basal and inducible transcription of the tyrosine hydroxylase gene are dependent upon a cAMP response element" J.Biol.Chem.268. 15689-15695 (1993)

[文献書誌] Weiser,M.: "Axotomy-induced differential gene induction in neurons of the locus ceruleus and substantia nigra." Brain Res.Mol.Brain Res.17. 319-327 (1993)

[文献書誌] Fraser,C.M.: "Beta-adrenergic and muscarinic cholinergic receptors:relationship between primary structure,receptor function and regulation" American Review of Respiratory Disease. 141. (1990)

[文献書誌] Venter,J.C.: "Isolation,purification and molecular biology of cell membrane receptors" Comprehensive Medicinal Chemistry. 3. (1990)

[文献書誌] Venter,J.C.: "Genome sequencing conference I:Summary" Genomics. 8. (1990)

[文献書誌] Usherwood,P.N.: "Channels formed:by M2 peptides of a putative glutamate receptor subunit of locust." EXS. 63. 241-249 (1993)

[文献書誌] Kerry,C.J.: "Reconstitution of glutamate receptor proteins purified from xenopus central nervous system into artificial bilayers." Mol.Pharmacol.44. 142-152 (1993)

[文献書誌] Webb,T.E.: "Cloning and functional expression of a brain G-proteincoupled ATP receptor." FEBS Lett.324. 219-225 (1993)

[文献書誌] Semba,J.: "Antiepileptic drug phrmacokinetics and neuropharmacokinetics in individual rats by repetitive withdrawal of blood and cerebrospinal fluid:milacemide." Br.J.Pharmacol.108. 1117-1124 (1993)

[文献書誌] Semba,J.: "Milacemide effcts on the temporal interrelationship of amino acids and monoamine metabolites in rat cerebrospinal fluid." European Journal of Pharmacology. 230. 321-326 (1993)

1993 年度実績報告書

鬼頭昭三放送大学, 教養学部, 教授 (00010140)