Study on pathoetilogy of schizophrenia and epilepsy fowsing on EAA newrons

基于EAA神经元的精神分裂症和癫痫的病理学研究

• 批准号: 03304036
• 负责人: TORU Michio
• 金额: $ 6.85万
• 依托单位: Tokyo Medical and Dental University, School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Co-operative Research (A)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03304036/
• 关键词: Exatatory amino acid; schizophrenia; epilepsy; phencyclidine; NMDA receptor; dopamine; newrotoxin; brain; メタンフェタミン; D-セリン; GABA; グリシン結合部位; NMDAレセプタ-複合体; ド-パミン; ジュロウグモ毒素; メタボトロピックレセプタ-

1. Glycine binding sites associated with NMDA receptors were increased in the cerebral cortex of postmortem brain of chronic schizophrenics, supporting the glutamate hypothesis of schizophrenia.2. NMDA receptors may give a tonic inhibition upon dopaminergic neurons through GABAergic interneurons in the rat medial frontal cortex.3. Abnormal behavior produced by NMDA antagonists was inhibited by the compunds which stimulate NMDA receptor function. D-serine, an agonist of NMDA receptors, was found to localize in the rat and human brain.4. A long-lasting increase in metabotropic receptor-coupled PI turnover was obserbed in the amygdala/piriform cortex of kindled rats, although no change in the contents of mRNA of metabotoropic receptors was found in the brain area. The long-lasting increase may play a role on the kindling mechanism.Intraventricular administation of quinolinic acid induces seizure, stimulating NMDA receptors. In addition, low dose and large dose of quinolinate may activate NO system and two types (L and T) Ca^<2+> channel, respectively.Increases in intracellular Ca^<2+> and glutamate-induced Ca^<2+> current through non-NMDA receptors, and abnormal PI turnover may be involved in the mechanism of delayd neuronal death.7. Large doses of methamphetamine produced reductions in dopamine and dopamine metabolites in the rat brain, stimulating glutamate transmission through NMDA receptors.There are heterogenous types of NMDA receptor complex in the rat brain, which were supported by the receptor binding experiements and by the measurements of DNA binding activities of transcription factors.

1。与NMDA受体相关的甘氨酸结合位点在慢性精神分裂症患者大脑的大脑皮层中增加，支持精神分裂症的谷氨酸假说2。 NMDA受体可以通过大鼠内侧额叶皮质中的GABA能神经元对多巴胺能神经元进行补品抑制。3。 NMDA拮抗剂产生的异常行为受到刺激NMDA受体功能的组合的抑制。 D-Serine是NMDA受体的激动剂，发现在大鼠和人脑中定位。4。在生物的大鼠的杏仁核/梨状皮层中观察到代谢受体偶联的PI周转率的长期增加，尽管在大脑区域中发现了代谢受体的mRNA内容物的变化。持久的增加可能在点燃机制中起作用。喹啉酸的脑电施用会诱导癫痫发作，刺激NMDA受体。此外，低剂量和大剂量的喹位酸酯可能会分别激活NO系统和两种类型（L和T）Ca^<2+>通道。在细胞内Ca^<2+>中increase，通过非NMDA受体通过非NMDA受体的谷氨酸诱导的CA^<2+电流，可能涉及PI延迟的pi neurond neuronyd neuronyd。大剂量的甲基苯丙胺可减少大鼠脑中多巴胺和多巴胺代谢产物的降低，刺激通过NMDA受体的刺激谷氨酸传播。大鼠脑中NMDA受体复合物的异源类型，这些类型的NMDA受体类型由受体结合​​体验和测量DNA结合因子的测量值支持，而这些型NMDA受体具有支持。

项目成果

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Yuji Yonezawa、Taka Matsumoto、Tetsuyuki Tsutsumi、Kaoru Nakamura、Makoto Hirano、Hisao Hondo、Kijiro Hashimoto、Hideyuki Uchimura、Tatsuo Nakahara：“苯环己哌啶对大鼠大脑中氨基酸的影响”神经化学 30. 500-501 (1991)。

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K.Ogita、T.Kouda、T.Suzuki、A.OhKawara、R.Enomoto、T.Nabeshima 和 Y.Yoneda：“SH 反应剂对 Triton 处理的脑突触膜中 [^3H] 谷氨酸结合的不同影响X-100”神经化学国际。18. 55-62 (1991)

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T.Ohmori, T.Kiyama, A.Muraki and I.Yamashita: "Competitive and noncompetition N-methyl-D-aspartits antagonists protect dopaminege and serfornergic newrofoxicity produce by methamphetamine invarious brain regions" J.Neural Transm.92. 97-106 (1993)

T.Ohmori、T.Kiyama、A.Muraki 和 I.Yamashita：“竞争性和非竞争性 N-甲基-D-天冬氨酸拮抗剂可保护甲基苯丙胺在各个脑区产生的多巴胺和神经神经毒性”J.Neural Transm.92。

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