1992 年度実績報告書

脳細胞機能・代謝・分子構築連関からみた軽度〜重度脳虚血とその治療的手段

研究課題

研究課題/領域番号	04304042
研究機関	新潟大学
研究代表者	下地恒毅新潟大学, 医学部, 教授 (30040158)
研究分担者	佐武明新潟大学, 脳研究所, 教授 (70018589) 熊西敏郎新潟大学, 脳研究所, 教授 (40018601) 佐藤公道京都大学, 薬学部, 教授 (80025709) 浅野孝雄埼玉医科大学, 総合医療センター, 教授 (70090496) 赤池紀生東北大学, 医学部, 教授 (30040182)
キーワード	脳虚血 / 細胞内カルシウム / 海馬 / 脳損傷 / 長期増強 / NMDAレセプター
研究概要	今年度はラット、マウスを用いたin vivoおよびin vitroの脳虚血モデル実験による脳虚血に対する低抗性の検索、脳内の各レセプターと脳虚血との関言に関する電気生理学的検索および分子生物学的検索を進めた。以下にこれまでに得られた主な知見を示す。 (1)光ファイバーを用いたfura-2蛍光法によりin vivoにおけるラット海馬細胞内Ca^<2+>農度変化の測定が可能となり、脳虚血時における同領域の細胞内Ca^<2+>濃度上昇が確認された。興味深いことに脳虚血モデルラットでは短時間の虚血を2度、3度と繰り反すと2、3度目では1度目の虚血に比較して細胞内Ca^<2+>濃度上昇が抑制されるとともに、虚血中平坦化した脳波が短時間で回復し、虚血の繰り反しにより虚血に対する抵抗性が高まることが示唆された。

研究成果
(24件)

すべてその他

すべて文献書誌 (24件)

[文献書誌] Karsuki,H et al.: "Involvement of postsynaptic G proteins in hippocampal long term potentiation." brain research. 581. 108-114 (1992)
[文献書誌] Karsuki,H et al.: "The involvement of muscarinic,β-adrenergic and metabotropic glutamate receprors in long-term potentiation in the fimbria-CA3 pathway of the hippocampus." Neuroscience litters. 142. 249-252 (1992)
[文献書誌] Ishihara,K et al.: "YM-14673,a new thyrotropin-releasihg hormone analon,augments long-term potentiation in the mossy fiber CA3 system of guinea pig hippocampal slices." J.pharmacobio-Dynamics. 15. 75-78 (1992)
[文献書誌] Ueda,M et al.: "bifemelane enhances high K^+-evoked release of glutamate from mossy fiber synaptosomes of guinea pig hippocampus." European journal of pharmacology. 219. 271-277 (1992)
[文献書誌] Kaneko,S et al.: "Metabotropic responses to acetylcholine and serotonin of Xenopus oocytes injected with rat brain mRNA are transduced by different G-protein subtypes." FEBS Litters. 299. 179-182 (1992)
[文献書誌] 佐藤公道: "脳内サイトカインの発見分布とその調節" BIO medica. 7. 1401-1405 (1992)
[文献書誌] K.Sakimrua,et al.: "Primary structure and expression of the γ2 subunit of the glutamate receptor channel selective for kainte." Neuron. 8. 267-274 (1992)
[文献書誌] T.Morita,et al.: "Cloning and functional expression of a cDNA encoding the mouse β2 subunit of the kainate-selective glutamate receptor channel." Mol.Brain Res.14. 143-146 (1992)
[文献書誌] H.Meguro,et al.: "Functional characterization of a heteromeric MNDA receptor channel expressed from cloned cDNAs." Nature. 357. 70-74 (1992)
[文献書誌] T.Kutsuwada,et al.: "Molecular diversity of the NMDA receptor channel." Nature. 358. 36-41 (1992)
[文献書誌] K.Ikeda,et al: "Cloning and expression of the ε4 subunit of the NMDA receptor channel." FEBS lett.313. 34-38 (1992)
[文献書誌] M.Watanabe,et al.: "Developmental changes in distribution of NMDA receptor channel subunit mRNAs." NeuroReport. 3. 1138-1140 (1992)
[文献書誌] Ueno,S at al.: "Proton-induced sodium current in freshly isolated hypothalamic neurones of the rat" J.Physiol.(London). 447. 309-327 (1992)
[文献書誌] Akaike,N et al.: "Tetrodotoxin-sensitive calcium-conducting channels in the rat hippocampal CA1 region" J.Physiol.(London). 450. 529-546 (1992)
[文献書誌] Uneyama,H et al: "Serotonin-operated potassium current in CA1 neurons dissociated for rat hippocampus" J.Neurophysiol.
[文献書誌] Kumanishi,T.eg al.: "Human glial fibrillary acidic protein(GFAP):molecular cloning of the complete cDNA seguence and chromosomal localization(chromosome 17)of the FGAP gene." Acta Neuropathol.83. 569-578 (1992)
[文献書誌] Araki,K.et al.: "Structure and expression of human and rat DaDtDtレriaCtDtレ dopamine receptor genes." Neurochem.Int.21. 91-98 (1992)
[文献書誌] 桃生勝巳他: "ヒト2',3'-cyclic-nucleotide 3'-phosphodiesterase遺伝子の構造と染色体局在." 神経化学. 31. 130-131 (1992)
[文献書誌] Kudo,Y et al.: "A single optical fiber fluorometric device for measurement of intra-Cellular Ca2+concentration:Its application to hippocampal neurons in vitro and in vivo" Neuroscience. 50. 619-625 (1992)
[文献書誌] Bito,H et al.: "Platelet-activating factor(PAF)receptor in rat brain:PAF nibukuzes ubtracekkykar Ca2+in hippocampal neurons" Neuron. 9. 285-294 (1992)
[文献書誌] Takagi H et al.: "The expression of presynaptic t ACPD receptor in rat cerebellum" Biocm.Biophys.Res.Comm. 189. 1287-1295 (1992)
[文献書誌] Suzuki,T et al.: "Calpain may produce a Ca2+-independent form of kinase C in longterm potentiation" Biocem.Biophys.Res.Comm.189. 1515-1520 (1992)
[文献書誌] Ogura,A et al.: "Further evidence for calcium permeability of non NMDA receptor channels in hippocampal neurons" Neurosci.Res.12. 606-616 (1992)
[文献書誌] Takagi,H et al.: "Delayed appearacence of G-protein coupled sugnal transduction system in developing cerebellular Purkinje cell dendrites" Neurosci.Res.15. 206-212 (1992)

1992 年度 実績報告書

脳細胞機能・代謝・分子構築連関からみた軽度〜重度脳虚血とその治療的手段

研究代表者

下地 恒毅 新潟大学, 医学部, 教授 (30040158)

研究成果

[文献書誌] Karsuki,H et al.: "Involvement of postsynaptic G proteins in hippocampal long term potentiation." brain research. 581. 108-114 (1992)

[文献書誌] Karsuki,H et al.: "The involvement of muscarinic,β-adrenergic and metabotropic glutamate receprors in long-term potentiation in the fimbria-CA3 pathway of the hippocampus." Neuroscience litters. 142. 249-252 (1992)

[文献書誌] Ishihara,K et al.: "YM-14673,a new thyrotropin-releasihg hormone analon,augments long-term potentiation in the mossy fiber CA3 system of guinea pig hippocampal slices." J.pharmacobio-Dynamics. 15. 75-78 (1992)

[文献書誌] Ueda,M et al.: "bifemelane enhances high K^+-evoked release of glutamate from mossy fiber synaptosomes of guinea pig hippocampus." European journal of pharmacology. 219. 271-277 (1992)

[文献書誌] Kaneko,S et al.: "Metabotropic responses to acetylcholine and serotonin of Xenopus oocytes injected with rat brain mRNA are transduced by different G-protein subtypes." FEBS Litters. 299. 179-182 (1992)

[文献書誌] 佐藤 公道: "脳内サイトカインの発見分布とその調節" BIO medica. 7. 1401-1405 (1992)

[文献書誌] K.Sakimrua,et al.: "Primary structure and expression of the γ2 subunit of the glutamate receptor channel selective for kainte." Neuron. 8. 267-274 (1992)

[文献書誌] T.Morita,et al.: "Cloning and functional expression of a cDNA encoding the mouse β2 subunit of the kainate-selective glutamate receptor channel." Mol.Brain Res.14. 143-146 (1992)

[文献書誌] H.Meguro,et al.: "Functional characterization of a heteromeric MNDA receptor channel expressed from cloned cDNAs." Nature. 357. 70-74 (1992)

[文献書誌] T.Kutsuwada,et al.: "Molecular diversity of the NMDA receptor channel." Nature. 358. 36-41 (1992)

[文献書誌] K.Ikeda,et al: "Cloning and expression of the ε4 subunit of the NMDA receptor channel." FEBS lett.313. 34-38 (1992)

[文献書誌] M.Watanabe,et al.: "Developmental changes in distribution of NMDA receptor channel subunit mRNAs." NeuroReport. 3. 1138-1140 (1992)

[文献書誌] Ueno,S at al.: "Proton-induced sodium current in freshly isolated hypothalamic neurones of the rat" J.Physiol.(London). 447. 309-327 (1992)

[文献書誌] Akaike,N et al.: "Tetrodotoxin-sensitive calcium-conducting channels in the rat hippocampal CA1 region" J.Physiol.(London). 450. 529-546 (1992)

[文献書誌] Uneyama,H et al: "Serotonin-operated potassium current in CA1 neurons dissociated for rat hippocampus" J.Neurophysiol.

[文献書誌] Kumanishi,T.eg al.: "Human glial fibrillary acidic protein(GFAP):molecular cloning of the complete cDNA seguence and chromosomal localization(chromosome 17)of the FGAP gene." Acta Neuropathol.83. 569-578 (1992)

[文献書誌] Araki,K.et al.: "Structure and expression of human and rat DaDtDtレriaCtDtレ dopamine receptor genes." Neurochem.Int.21. 91-98 (1992)

[文献書誌] 桃生 勝巳 他: "ヒト2',3'-cyclic-nucleotide 3'-phosphodiesterase遺伝子の構造と染色体局在." 神経化学. 31. 130-131 (1992)

[文献書誌] Kudo,Y et al.: "A single optical fiber fluorometric device for measurement of intra-Cellular Ca2+concentration:Its application to hippocampal neurons in vitro and in vivo" Neuroscience. 50. 619-625 (1992)

[文献書誌] Bito,H et al.: "Platelet-activating factor(PAF)receptor in rat brain:PAF nibukuzes ubtracekkykar Ca2+in hippocampal neurons" Neuron. 9. 285-294 (1992)

[文献書誌] Takagi H et al.: "The expression of presynaptic t ACPD receptor in rat cerebellum" Biocm.Biophys.Res.Comm. 189. 1287-1295 (1992)

[文献書誌] Suzuki,T et al.: "Calpain may produce a Ca2+-independent form of kinase C in longterm potentiation" Biocem.Biophys.Res.Comm.189. 1515-1520 (1992)

[文献書誌] Ogura,A et al.: "Further evidence for calcium permeability of non NMDA receptor channels in hippocampal neurons" Neurosci.Res.12. 606-616 (1992)

[文献書誌] Takagi,H et al.: "Delayed appearacence of G-protein coupled sugnal transduction system in developing cerebellular Purkinje cell dendrites" Neurosci.Res.15. 206-212 (1992)

1992 年度実績報告書

下地恒毅新潟大学, 医学部, 教授 (30040158)

[文献書誌] 佐藤公道: "脳内サイトカインの発見分布とその調節" BIO medica. 7. 1401-1405 (1992)

[文献書誌] 桃生勝巳他: "ヒト2',3'-cyclic-nucleotide 3'-phosphodiesterase遺伝子の構造と染色体局在." 神経化学. 31. 130-131 (1992)