1993 年度実績報告書

興奮性アミノ酸ニューロンを指標とした分裂病とてんかんの病因に関する研究

研究課題

研究課題/領域番号	03304036
研究機関	東京医科歯科大学
研究代表者	融道男東京医科歯科大学, 医学部, 教授 (20013972)
研究分担者	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, 教授 (10113557)
キーワード	興奮性アミノ酸 / 精神分裂病 / てんかん / メタンフェタミン / フェンシクリジン / D-セリン / GABA / NMDAレセプター
研究概要	1.前頭前野において、NMDAレセプターとGABAニューロンとの間に相互作用があることが、in vivo microdialysis法によって、確かめられた。 2.スナネズミを用いた脳虚血モデルにおいて、海馬CA1錐体細胞のシナプス後電位で、non-NMDA型レセプターでCA^<2+>透過性を示すグルタミン酸成分が増加していることが、新しく分かった。 3.メタアンフェタミンの線条体におけるドーパミン神経毒性に、メタアンフェタミン反復投与によるグルタミン酸の遅延性持続性の増加が、関与している可能性が示唆された。 4.キノリン酸脳室内投与によるけいれんが、L型Ca^<2+>チャンネル及びT型Ca^<2+>チャンネル拮抗薬で抑制されること、ニッケルやニカルジピンによっては部分的に抑制されることが分かった。 5.In vivo microdialysis法を用いた研究で、ラット線条体において、AMPA受容体はドーパミン遊離に促進的に作用していることが示された。 6.NMDA投与により、AP1結合蛋白は海馬において著明に、大脳皮質、線条体、視床下部及び橋・延髄においても増加すること、さらに、CREB結合蛋白が海馬で有意に増加することが分かった。 7.Phencyclidineの慢性投与で、大脳皮質と海馬のベンゾジアゼピン結合部位が増加し、嗅皮質では減少することがわかり、興奮性アミノ酸とGABAaレセプターとの間に相互作用があることが示唆された。 8.内因性 D-セリンの遊離に関して、in vivo dialysis micro法を用いて調べたが、ベラトリジン誘発による遊離は見られず、D-セリンの遊離は古典的な神経伝達物質とは、異なることがわかった。

研究成果
(22件)

すべてその他

すべて文献書誌 (22件)

[文献書誌] A.Hashimoto et al.,: "Endogenous D-serine in rat brain:N-methyl-D-aspartate receptor-related distribution and aging" J.of Neurochemistry. 60. 783-786 (1993)
[文献書誌] A.Hashimoto et al.,: "Embryonic development and postnatal changes in free D-aspartate and D-serine in the human prefrontal cortex" J.of Neurochemistry. 61. 348-351 (1993)
[文献書誌] A.Miwa et al.,: "Prestnaptic glutamate receptors depress inhibitory postsynaptic transmission in lobster neuromuscular synapse." J.of Neurophysialogy. 70. 1159-1167 (1993)
[文献書誌] K.Shimazaki et al.,: "Changes in inosital 1,4,5-tri phosphate-3-kinase immuno-reactivity following transient ischameia in gerbil hippocampus." Neuroreport. (in press).
[文献書誌] H.Tsubokawa et al.,: "Inosital 1,3,4,5-tetrakisphiphcte (2P_4)as a mediator of neuronal death in ischemic hippocampus" Neurosaince. (in press).
[文献書誌] H.Tsubokawa et al.,: "Ca^<2+>-dependent non-NMDA receptor-midoated synaptic currents in ischamic CA1 hippocampal neurons" J.Neurophysialogy. (in press).
[文献書誌] Y.Yonezawa et al.,: "Effect of phencycliceine on endogenous exitatory amino acid release from the rat anterior cingulate cortex- as in vivo microdialysis study" J.Neural Transmission. 94. 235-240 (1993)
[文献書誌] H.Hondo et al.,: "Effect of phencycliceine on dopamine release in the rat pregrontal cortex an in vivo microdialysis study" Brain Research. 633. 337-342 (1993)
[文献書誌] M.Hikiji et al.,: "Increase of kainate receptor mRNA in the hippocampus CA3 of amygdalin-kiedled rats detected by in sith hybridization" Life Sainces. 53. 857-864 (1993)
[文献書誌] H.Tomita et al.,: "Changes of dopamine D_2 and GluR-1 glutamate receptor mRNA in the brain of phencyclidine-treated rats" Acta Medica Okayama. (in press).
[文献書誌] K.Ogita and Y.Yoneda: "Selective potentiation of DNA binding activities of both AP1 and CREB through in vivo activation of NMDA receptor complex in mouse brain" J of Neurochemistry. (in press).
[文献書誌] Y.Yoneda et al.,: "Differential profiles of binding of a radiolabeled agonist and antagonist at a glycine recognition domain on the NMDA receptor" J.of Neurochemistry. 62. 102-112 (1994)
[文献書誌] P.Zuo et al.,: "Further evidence for multiple bons of on NMDA recognition domein in rat brain using membrane bincling techniques" J of Neurochemistry. 61. 1865-1823 (1993)
[文献書誌] T.Ohmori et al.,: "Competitive and noncompetitive NMDA antagonists protect dopaminergic and serotonergic neurotoxiuty prodaced by methamphetamine in various brain region" J of Neural Transmission. 92. 97-106 (1993)
[文献書誌] T.Ohmori et al.,: "Competitive and noncompetitive NMDA antagonists block sensitization to methamphetamine" Pharmacol.Biochem.Behan. (in press).
[文献書誌] T.Abekawa et al.,: "Effects of repeated administration of a high cose of methamphetamine on DA and glutamate velease in rat striatum and N.accumbens" Brain Reseuch. (in press).
[文献書誌] M.Hasegawa et al.,: "MK-801 increases endogenous aatylcholine release in the rat paristal coterp:a study using brain microdialysis" Neurosaince Letters. 150. 53-56 (1993)
[文献書誌] T.Kuzuya et al.,: "Effects of anti-epileptic drugs on serum zinc and copper concentrations in epileptic patients" Clin.Pharmacol.Ther.Toxicol.31. 61-65 (1993)
[文献書誌] T.Nabeshima et al.,: "The inhibitory effects of salmon calcitonin on introthecally injected NMDA-inducer aver sive clrharior in mice" Res.Comm.Chem.Pathol.Phavpocol. (in press).
[文献書誌] T.Maurice et al.,: "Low close of DTG attenuetes MK-801-induced spatial working memory impairment in mice" Psychopfasmaroclogy. (in press).
[文献書誌] H.Kinoshita et al: "Effect of MK-801 on the catalepsy in cluced by △9-tetrahydorocannabinol in mice" J.Weural Transmission. (in press).
[文献書誌] M.Ishomaru et al.,: "In croases in strychnine-insensitive glycine binding sites in cerebral cortex of chronic schizophrenics:evidence for glatamate hypothesis" Biological Psychiatry. (in press).

1993 年度 実績報告書

興奮性アミノ酸ニューロンを指標とした分裂病とてんかんの病因に関する研究

研究代表者

融 道男 東京医科歯科大学, 医学部, 教授 (20013972)

研究成果

[文献書誌] A.Hashimoto et al.,: "Endogenous D-serine in rat brain:N-methyl-D-aspartate receptor-related distribution and aging" J.of Neurochemistry. 60. 783-786 (1993)

[文献書誌] A.Hashimoto et al.,: "Embryonic development and postnatal changes in free D-aspartate and D-serine in the human prefrontal cortex" J.of Neurochemistry. 61. 348-351 (1993)

[文献書誌] A.Miwa et al.,: "Prestnaptic glutamate receptors depress inhibitory postsynaptic transmission in lobster neuromuscular synapse." J.of Neurophysialogy. 70. 1159-1167 (1993)

[文献書誌] K.Shimazaki et al.,: "Changes in inosital 1,4,5-tri phosphate-3-kinase immuno-reactivity following transient ischameia in gerbil hippocampus." Neuroreport. (in press).

[文献書誌] H.Tsubokawa et al.,: "Inosital 1,3,4,5-tetrakisphiphcte (2P_4)as a mediator of neuronal death in ischemic hippocampus" Neurosaince. (in press).

[文献書誌] H.Tsubokawa et al.,: "Ca^<2+>-dependent non-NMDA receptor-midoated synaptic currents in ischamic CA1 hippocampal neurons" J.Neurophysialogy. (in press).

[文献書誌] Y.Yonezawa et al.,: "Effect of phencycliceine on endogenous exitatory amino acid release from the rat anterior cingulate cortex- as in vivo microdialysis study" J.Neural Transmission. 94. 235-240 (1993)

[文献書誌] H.Hondo et al.,: "Effect of phencycliceine on dopamine release in the rat pregrontal cortex an in vivo microdialysis study" Brain Research. 633. 337-342 (1993)

[文献書誌] M.Hikiji et al.,: "Increase of kainate receptor mRNA in the hippocampus CA3 of amygdalin-kiedled rats detected by in sith hybridization" Life Sainces. 53. 857-864 (1993)

[文献書誌] H.Tomita et al.,: "Changes of dopamine D_2 and GluR-1 glutamate receptor mRNA in the brain of phencyclidine-treated rats" Acta Medica Okayama. (in press).

[文献書誌] K.Ogita and Y.Yoneda: "Selective potentiation of DNA binding activities of both AP1 and CREB through in vivo activation of NMDA receptor complex in mouse brain" J of Neurochemistry. (in press).

[文献書誌] Y.Yoneda et al.,: "Differential profiles of binding of a radiolabeled agonist and antagonist at a glycine recognition domain on the NMDA receptor" J.of Neurochemistry. 62. 102-112 (1994)

[文献書誌] P.Zuo et al.,: "Further evidence for multiple bons of on NMDA recognition domein in rat brain using membrane bincling techniques" J of Neurochemistry. 61. 1865-1823 (1993)

[文献書誌] T.Ohmori et al.,: "Competitive and noncompetitive NMDA antagonists protect dopaminergic and serotonergic neurotoxiuty prodaced by methamphetamine in various brain region" J of Neural Transmission. 92. 97-106 (1993)

[文献書誌] T.Ohmori et al.,: "Competitive and noncompetitive NMDA antagonists block sensitization to methamphetamine" Pharmacol.Biochem.Behan. (in press).

[文献書誌] T.Abekawa et al.,: "Effects of repeated administration of a high cose of methamphetamine on DA and glutamate velease in rat striatum and N.accumbens" Brain Reseuch. (in press).

[文献書誌] M.Hasegawa et al.,: "MK-801 increases endogenous aatylcholine release in the rat paristal coterp:a study using brain microdialysis" Neurosaince Letters. 150. 53-56 (1993)

[文献書誌] T.Kuzuya et al.,: "Effects of anti-epileptic drugs on serum zinc and copper concentrations in epileptic patients" Clin.Pharmacol.Ther.Toxicol.31. 61-65 (1993)

[文献書誌] T.Nabeshima et al.,: "The inhibitory effects of salmon calcitonin on introthecally injected NMDA-inducer aver sive clrharior in mice" Res.Comm.Chem.Pathol.Phavpocol. (in press).

[文献書誌] T.Maurice et al.,: "Low close of DTG attenuetes MK-801-induced spatial working memory impairment in mice" Psychopfasmaroclogy. (in press).

[文献書誌] H.Kinoshita et al: "Effect of MK-801 on the catalepsy in cluced by △9-tetrahydorocannabinol in mice" J.Weural Transmission. (in press).

[文献書誌] M.Ishomaru et al.,: "In croases in strychnine-insensitive glycine binding sites in cerebral cortex of chronic schizophrenics:evidence for glatamate hypothesis" Biological Psychiatry. (in press).

1993 年度実績報告書

融道男東京医科歯科大学, 医学部, 教授 (20013972)