1992 Fiscal Year Annual Research Report

興奮性アミノ酸ニューロンを指様とした分裂病とてんかんの病因に関する研究

Research Project

Project/Area Number	03304036
Research Institution	Tokyo Medical and Dental University
Principal Investigator	融道男東京医科歯科大学, 医学部, 教授 (20013972)
Co-Investigator(Kenkyū-buntansha)	秋山一文岡山大学, 医学部, 助手 (40150990) 米田幸雄摂南大学, 薬学部, 助教授 (50094454) 西川徹国立精神, 神経センター・神経研究所, 室長 (00198441) 川合述史自治医科大学, 第一生理学教室, 教授 (00073065) 小山司北海道大学, 医学部, 助教授 (10113557)
Keywords	興奮性アミノ酸 / 精神分裂病 / てんかん / NMDAレセプター / グリシン結合部位 / D-セリン / メタンフェタミン / フェンシクリジン
Research Abstract	1.メタンフェタミン逆耐性ラットに、フェンシクリジンを投与すると行動学的(spontaneous activity,head weaving)に交差逆耐性がみられ、前頭前野皮質および前部帯状回皮質においてアスバラギン酸合量が著明に減少することがわかった。 2.扁桃核キンドリングラットの海馬において、Kainate受容体(KA-1)のmRNAが増加し、NMDA受容体(NMDARI)およびAMPA受容体(GluR-2)のmRNAには変化がないことを見出した。 3.NMDAレセプター複合体内に存在するグリシン結合部位に内在性ポリアミンに対する反応の異なるアゴニスト選択型とアンタゴニスト選択型が存在する可能性を示唆する研究結果が得られた。 4.NMDAレセプター複合体のグリシン結合部位に対するアゴニストであるD-セリンがラットやヒトの脳に器官特異的に存在していることを、世界ではじめて発見し、ならびに、その測定方法を確立した。 5.慢性分裂病死後脳の大脳皮質の6部位で、グリシン結合部位の結合親和性には変化はないが、最大結合数が増加していることがわかり、精神分裂病における興奮性アミノ酸神経伝達異常が杉在することの証拠の一つを発見した。 6.ラットに多量のメタンフェタミンを多量投与すると脳内のセロトニン含量が減少するが、これをNMDAアンタゴニストが抑制することから、メタンフェタミンのセロトニンニューロンに対する神経毒性にNMDAレセプターが関与していることが示唆された。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] M.Toru,A.Kurumaji,S.Kumashiro,I.Suga,M.Takashima,T.Nishikawa: "Exatatory amino acidepir neapnes in chnnie schizophrenic brain" Molewlar Neuropharmucology. 2. 241-243 (1992)
[Publications] A.Watanabe,J.Semba,A.Kurumaji,S.Kumashima,M.Toru: "Measurement of glutamate,aspartate and glycine and its potential precursors in human brain using high-performasion liquid chnmitography by pre-column deriratization with DABS-1" Joutnal of Chromatogtaphy. 583. 241-245 (1992)
[Publications] 石丸昌彦,車地暁生,融道男: "慢性分裂病死後脳の大脳皮質におけるストリキニン非感受性グリシン結合部位に関する研究" 脳と精神の医学. 3. 315-319 (1992)
[Publications] H.Ishimaru,A.Kato,H.Suzuki,T.Fukuta,T.Kameyama,T.Nabeshima: "Effects of N-methyl-D-aspartate recepter antagonists on carbon menoxide-inducect brain damage in mice" The Journal of Pharmacology and Expenmental Therapeutics. 261. 349-352 (1992)
[Publications] Y.Maeda,T.Nakamura,T.Hasegawa,H.Furukawa,T.Nabeshima: "Effect of Salmen calutonin on the lethality of quinalinic acil,on excitatory amino auid" Research Communications in Chemical Pathalogy and Pharmaulogy. 77. 191-199 (1992)
[Publications] K.Shimazaki,H.PC.Robinson,T.Nakajima,N.Kawai,T.Takenawa: "Purification of AMPA type glutamate receptor by a spicler toxin" Molecular Brain Resrach. 13. 331-337 (1992)
[Publications] K.Akiyama,A.Daigen,N.Yamada et al: "Long-lasting enhancement of metabotropic excitatory amino aacl recepter-mecliatecl polyphosphoinositicle hydrolysis in the amygdala/pirijom corters of deep prepiriform cortical kindled rats" Brain Research. 569. 71-77 (1992)
[Publications] H.Ujike,H.Tsuchida,A.Kanzaki,K.Akiyama,S.Otsuki: "Competitive and non-competitive NMDA antagomists fail to prevenl the induction of mithamphetamine-indrad sensitization" Life Sciences. 50. 1673-1681 (1992)
[Publications] T.Kuroki,Y.Tatebayashi,K.Ide etal: "Antagemism of ceruleticle,a cholecystokinin analog,to the neurochemical effects of the non-cempetitive NMDA receptor on tagonists phencyclidine and MK-801,on rigional clpaminergie neurons in the rat erain," Neuropepticies. 21. 167-173 (1992)
[Publications] T.Ohmori,T.Koyama,F.Nakamura,P.Wang,I.Yamashita: "Effect of phencyclidine on spontaneous and NMDA-indiced eddluox of dipamine from super fused slias of rat striatum" Neuropharmacology. 31. 461-467 (1992)
[Publications] T.Ohmori,F.Nakamura,T.Koyama,I.Yamashita: "Amygdala kindling dees not alter the NMDA receptor-channel cemplex which mednlates dopamine release in the rat striatum and amygdala" Brain Research. 587. 257-262 (1992)
[Publications] A.Muraki,T.Koyama,M.Nakayama,T.Ohmori,T.Yamashita: "MK-801,a men-compctitive antafonist of NMDA recrptor,prevents methamphetamine-induced clecrease of striatal depamine uptake sites in the rat striatum" Neuroscience Letters. 136. 39-42 (1992)
[Publications] H.Tsubokawa,K.Oguro,H.PC.Rebinson,T.Masuazawa,T.Kirino,N.Kawai: "Abnormal Ca^<2+> homeostasis before cell death revealecl by whole cell recerding of ischemic CAI hippocampal neurons" Neurodcience. 49. 807-817 (1992)
[Publications] T.Kirino,H.P.C.Robinson,A.Miwa,A.Tamura,N.Kawai: "Disturbana of membrane function preceding ischemic delayed neuranal death in the gerbil hippocumpas" Journal of Cerebral Blood Flow and Metabelison. 12. 408-417 (1992)
[Publications] A.Hashimoto,T.Nishikawa,T.Oka,K.Takahashi,T.Hayashi: "Determination of free amino and enantiomers in rat brain and serum by high-performana liquid chromatography after derivatization with N-terti-butyloxycarbonyl-L-cysteine" Journal of Chromatography. 582. 41-48 (1992)
[Publications] 西川徹,橋本篤司,谷井晴之,海野麻未,岡高恵,柏淳,岩間久行,高橋清之: "フェンサイクリジンの脳に対する作用" 精神医学. 34. 891-900 (1992)
[Publications] R.Enomoto,K.Ogita,Y.Yoneda: "Differential pitentiation by spermidine of abilities of a variety of displacers for[ ^3H]MK-801 bincling in hippecampal synaptic menbranes" Neuroscience Research.
[Publications] K.Akiyama,Y.Yoneda,K.Ogita etal: "Ionotropic exatatory amino and receptors in discrate brain regions of kindled rats" Brain Reserch. 587. 73-82 (1992)

1992 Fiscal Year Annual Research Report

興奮性アミノ酸ニューロンを指様とした分裂病とてんかんの病因に関する研究

Principal Investigator

融 道男 東京医科歯科大学, 医学部, 教授 (20013972)

Research Products

[Publications] M.Toru,A.Kurumaji,S.Kumashiro,I.Suga,M.Takashima,T.Nishikawa: "Exatatory amino acidepir neapnes in chnnie schizophrenic brain" Molewlar Neuropharmucology. 2. 241-243 (1992)

[Publications] A.Watanabe,J.Semba,A.Kurumaji,S.Kumashima,M.Toru: "Measurement of glutamate,aspartate and glycine and its potential precursors in human brain using high-performasion liquid chnmitography by pre-column deriratization with DABS-1" Joutnal of Chromatogtaphy. 583. 241-245 (1992)

[Publications] 石丸 昌彦,車地 暁生,融 道男: "慢性分裂病死後脳の大脳皮質におけるストリキニン非感受性グリシン結合部位に関する研究" 脳と精神の医学. 3. 315-319 (1992)

[Publications] H.Ishimaru,A.Kato,H.Suzuki,T.Fukuta,T.Kameyama,T.Nabeshima: "Effects of N-methyl-D-aspartate recepter antagonists on carbon menoxide-inducect brain damage in mice" The Journal of Pharmacology and Expenmental Therapeutics. 261. 349-352 (1992)

[Publications] Y.Maeda,T.Nakamura,T.Hasegawa,H.Furukawa,T.Nabeshima: "Effect of Salmen calutonin on the lethality of quinalinic acil,on excitatory amino auid" Research Communications in Chemical Pathalogy and Pharmaulogy. 77. 191-199 (1992)

[Publications] K.Shimazaki,H.PC.Robinson,T.Nakajima,N.Kawai,T.Takenawa: "Purification of AMPA type glutamate receptor by a spicler toxin" Molecular Brain Resrach. 13. 331-337 (1992)

[Publications] K.Akiyama,A.Daigen,N.Yamada et al: "Long-lasting enhancement of metabotropic excitatory amino aacl recepter-mecliatecl polyphosphoinositicle hydrolysis in the amygdala/pirijom corters of deep prepiriform cortical kindled rats" Brain Research. 569. 71-77 (1992)

[Publications] H.Ujike,H.Tsuchida,A.Kanzaki,K.Akiyama,S.Otsuki: "Competitive and non-competitive NMDA antagomists fail to prevenl the induction of mithamphetamine-indrad sensitization" Life Sciences. 50. 1673-1681 (1992)

[Publications] T.Kuroki,Y.Tatebayashi,K.Ide etal: "Antagemism of ceruleticle,a cholecystokinin analog,to the neurochemical effects of the non-cempetitive NMDA receptor on tagonists phencyclidine and MK-801,on rigional clpaminergie neurons in the rat erain," Neuropepticies. 21. 167-173 (1992)

[Publications] T.Ohmori,T.Koyama,F.Nakamura,P.Wang,I.Yamashita: "Effect of phencyclidine on spontaneous and NMDA-indiced eddluox of dipamine from super fused slias of rat striatum" Neuropharmacology. 31. 461-467 (1992)

[Publications] T.Ohmori,F.Nakamura,T.Koyama,I.Yamashita: "Amygdala kindling dees not alter the NMDA receptor-channel cemplex which mednlates dopamine release in the rat striatum and amygdala" Brain Research. 587. 257-262 (1992)

[Publications] A.Muraki,T.Koyama,M.Nakayama,T.Ohmori,T.Yamashita: "MK-801,a men-compctitive antafonist of NMDA recrptor,prevents methamphetamine-induced clecrease of striatal depamine uptake sites in the rat striatum" Neuroscience Letters. 136. 39-42 (1992)

[Publications] H.Tsubokawa,K.Oguro,H.PC.Rebinson,T.Masuazawa,T.Kirino,N.Kawai: "Abnormal Ca^<2+> homeostasis before cell death revealecl by whole cell recerding of ischemic CAI hippocampal neurons" Neurodcience. 49. 807-817 (1992)

[Publications] T.Kirino,H.P.C.Robinson,A.Miwa,A.Tamura,N.Kawai: "Disturbana of membrane function preceding ischemic delayed neuranal death in the gerbil hippocumpas" Journal of Cerebral Blood Flow and Metabelison. 12. 408-417 (1992)

[Publications] A.Hashimoto,T.Nishikawa,T.Oka,K.Takahashi,T.Hayashi: "Determination of free amino and enantiomers in rat brain and serum by high-performana liquid chromatography after derivatization with N-terti-butyloxycarbonyl-L-cysteine" Journal of Chromatography. 582. 41-48 (1992)

[Publications] 西川 徹,橋本 篤司,谷井 晴之,海野 麻未,岡 高恵,柏 淳,岩間 久行,高橋 清之: "フェンサイクリジンの脳に対する作用" 精神医学. 34. 891-900 (1992)

[Publications] R.Enomoto,K.Ogita,Y.Yoneda: "Differential pitentiation by spermidine of abilities of a variety of displacers for[ ^3H]MK-801 bincling in hippecampal synaptic menbranes" Neuroscience Research.

[Publications] K.Akiyama,Y.Yoneda,K.Ogita etal: "Ionotropic exatatory amino and receptors in discrate brain regions of kindled rats" Brain Reserch. 587. 73-82 (1992)

融道男東京医科歯科大学, 医学部, 教授 (20013972)

[Publications] 石丸昌彦,車地暁生,融道男: "慢性分裂病死後脳の大脳皮質におけるストリキニン非感受性グリシン結合部位に関する研究" 脳と精神の医学. 3. 315-319 (1992)

[Publications] 西川徹,橋本篤司,谷井晴之,海野麻未,岡高恵,柏淳,岩間久行,高橋清之: "フェンサイクリジンの脳に対する作用" 精神医学. 34. 891-900 (1992)