1997 Fiscal Year Annual Research Report

一酸化窒素を介するグルタミン酸神経毒性に対するニューロトロフィンの保護機構

Research Project

Project/Area Number	09470502
Research Institution	Kyoto University
Principal Investigator	赤池昭紀京都大学, 薬学研究科, 教授 (80135558)
Co-Investigator(Kenkyū-buntansha)	前田武彦京都大学, 薬学研究科, 助手 (50271010)
Keywords	ニューロトロフィン / 脳由来神経栄養因子 / グルタミン酸 / 神経細胞死 / 初代培養神経細胞 / 大脳皮質 / 一酸化窒素 / NMDA受容体
Research Abstract	大脳皮質における一酸化窒素(NO)神経毒性の機序を明らかにすること、またNOを介するグルタミン酸神経毒性に対する脳由来神経栄養因子(BDNF)の神経保護作用を明らかにする目的で、ラット胎仔由来大脳皮質ニューロンを用いた研究を行った。グルタミン酸の短時間投与により遅延性神経細胞死が誘発された。このグルタミン酸神経毒性は培地からのCa^<2+>の除去、NMDA受容体拮抗薬であるMK-801および一酸化窒素合成阻害薬であるN^ω-nitro-L-arginineの投与により抑制された。またグルタミン酸神経毒性はBDNFの前投与により濃度および時間依存的に抑制された。BDNFの投与によりBDNFに対する高親和性受容体であるTrkBのチロシンリン酸化が誘発された。カルシウムイオノフォアであるイオノマイシン、NOドナーであるS-nitrosocysteineおよびperoxynitriteを生成するSIN-1の投与により神経細胞死が引き起こされた。これらの神経毒性はいずれもBDNFの前投与により抑制された。以上の結果は、BDNFがNOの細胞毒性を減弱することによりNMDA受容体を介するグルタミン酸神経毒性を抑制することを示唆する。

Research Products
(15 results)

All Other

All Publications (15 results)

[Publications] Kaneda,K.et al: "Effects of B vitamins on glutamate-induced neurotoxicity in retinal cultures." Eur.J.Pharmacol.322. 259-264 (1997)
[Publications] Kume,T.et al: "BDNF prevents NO mediated glutamate cytotoxicity in cultured cortical neurons." Brain Res.756. 200-204 (1997)
[Publications] Kume,T.et al: "Ether extract of fetal calf serum protects cultured rat cortical neurons against glutamate cytotoxicity." Jpn.J.Pharmacol.73. 371-374 (1997)
[Publications] Maeda,T.et al: "Direct evidence for increase in excitatiory amino acids release during mossy fiber LTP in rat hippocampal slices as revealed by the patch sensor methods." Neurosci.Lett.224. 103-106 (1997)
[Publications] Kihara,T.et al: "Nicotinic receptor stimulation protects neurons against β-amyloid toxicity." Ann.Neurol.42. 159-163 (1997)
[Publications] Takami,S.et al: "Induction of macrophage inflammatory protein MIP-1α mRNA on glial cells after focal cerebral ischemia in the rat." Neurosci.Lett.227. 173-176 (1997)
[Publications] Kaneko,S.et al: "Nicotine protects cultured cortical neurons against glutamate-induced cytotoxicity via α7-neuronal receptors and neuronal CNS receptors." Brain Res.765. 135-140 (1997)
[Publications] Morizane,C.et al: "N^ω-Nitro-L-arginine methyl ester protects retinal neurons against N-methyI-D-aspartate-induced neurotoxicity in vivo." Eur.J.Pharmacol.328. 45-49 (1997)
[Publications] Kaneko,S.et al: "Inhibition of Ca^<2+> channel current by μ- and κ-opioid receptors coexpressed in Xenopus oocytes : desensitization dependence on Ca^<2+> channel al subunits." Br.J.Pharmacol.121. 806-812 (1997)
[Publications] Shimoshige,Y.et al: "Involvement of M2 receptor in an enhancement of long-term potentiation by carbachol in Schaffer collateral-CA1 synapses of hippocampal slices." Neurosci.Res.27. 175-180 (1997)
[Publications] Saji,H.et al: "Brain permeable zinc complex with neuroprotective action." STP Pharma Sciences. 7. 92-97 (1997)
[Publications] Tsujiyama,S.et al: "Potentiation by ethanol of GABA-induced current and facilitation of its desensitization on cultured rat cortical neurons." Gen.Pharmacol.28. 365-380 (1997)
[Publications] Kikuchi,M.et al: "Protective effects of methylcobalamin,a vitamin B_<12> analog,against glutamate neurotoxicity in retinal cell culture." Inv.Ophtahlmol.Vis.Sci.38. 848-854 (1997)
[Publications] Maeda,T.et al: "L-DOPA neurotoxicity is mediated by glutamate release in cultured rat striatal neurons." Brain Res.771. 159-162 (1997)
[Publications] 赤池昭紀: "ファルマシア" 神経に対するNO作用の二面性, 502-506 (1997)

1997 Fiscal Year Annual Research Report

一酸化窒素を介するグルタミン酸神経毒性に対するニューロトロフィンの保護機構

Principal Investigator

赤池 昭紀 京都大学, 薬学研究科, 教授 (80135558)

Research Products

[Publications] Kaneda,K.et al: "Effects of B vitamins on glutamate-induced neurotoxicity in retinal cultures." Eur.J.Pharmacol.322. 259-264 (1997)

[Publications] Kume,T.et al: "BDNF prevents NO mediated glutamate cytotoxicity in cultured cortical neurons." Brain Res.756. 200-204 (1997)

[Publications] Kume,T.et al: "Ether extract of fetal calf serum protects cultured rat cortical neurons against glutamate cytotoxicity." Jpn.J.Pharmacol.73. 371-374 (1997)

[Publications] Maeda,T.et al: "Direct evidence for increase in excitatiory amino acids release during mossy fiber LTP in rat hippocampal slices as revealed by the patch sensor methods." Neurosci.Lett.224. 103-106 (1997)

[Publications] Kihara,T.et al: "Nicotinic receptor stimulation protects neurons against β-amyloid toxicity." Ann.Neurol.42. 159-163 (1997)

[Publications] Takami,S.et al: "Induction of macrophage inflammatory protein MIP-1α mRNA on glial cells after focal cerebral ischemia in the rat." Neurosci.Lett.227. 173-176 (1997)

[Publications] Kaneko,S.et al: "Nicotine protects cultured cortical neurons against glutamate-induced cytotoxicity via α7-neuronal receptors and neuronal CNS receptors." Brain Res.765. 135-140 (1997)

[Publications] Morizane,C.et al: "N^ω-Nitro-L-arginine methyl ester protects retinal neurons against N-methyI-D-aspartate-induced neurotoxicity in vivo." Eur.J.Pharmacol.328. 45-49 (1997)

[Publications] Kaneko,S.et al: "Inhibition of Ca^<2+> channel current by μ- and κ-opioid receptors coexpressed in Xenopus oocytes : desensitization dependence on Ca^<2+> channel al subunits." Br.J.Pharmacol.121. 806-812 (1997)

[Publications] Shimoshige,Y.et al: "Involvement of M2 receptor in an enhancement of long-term potentiation by carbachol in Schaffer collateral-CA1 synapses of hippocampal slices." Neurosci.Res.27. 175-180 (1997)

[Publications] Saji,H.et al: "Brain permeable zinc complex with neuroprotective action." STP Pharma Sciences. 7. 92-97 (1997)

[Publications] Tsujiyama,S.et al: "Potentiation by ethanol of GABA-induced current and facilitation of its desensitization on cultured rat cortical neurons." Gen.Pharmacol.28. 365-380 (1997)

[Publications] Kikuchi,M.et al: "Protective effects of methylcobalamin,a vitamin B_<12> analog,against glutamate neurotoxicity in retinal cell culture." Inv.Ophtahlmol.Vis.Sci.38. 848-854 (1997)

[Publications] Maeda,T.et al: "L-DOPA neurotoxicity is mediated by glutamate release in cultured rat striatal neurons." Brain Res.771. 159-162 (1997)

[Publications] 赤池昭紀: "ファルマシア" 神経に対するNO作用の二面性, 502-506 (1997)

赤池昭紀京都大学, 薬学研究科, 教授 (80135558)