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盐可能会激活NO系统和两种类型（L和T）Ca^<2+>通道。细胞内Ca^<2+>和谷氨酸诱导的Ca^<2+ >通过非NMDA受体的电流和PI异常转移可能与延迟神经元死亡的机制有关7。大剂量的甲基苯丙胺在大鼠脑中的多巴胺和多巴胺代谢产生中降低，刺激通过NMDA受体的谷氨酸传播。大鼠脑中NMDA受体复合物的异源类型，这些类型是由受体结合​​和DNA测量的dna支持的。转录因子的结合活性。

项目成果

米沢 裕次,松本 孝,堤 哲之,中村 薫,平野 誠,本藤 久雄,橋本 喜次郎,内村 英幸,中原 辰雄: "フェンサイクリジンのラット脳内アミノ酸への影響" 神経化学. 30. 500-501 (1991)

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)。

K.Ogita,T.Kouda,T.Suzuki,A.OhKawara,R.Enomoto,T.Nabeshima & Y.Yoneda: "Differential effects of SH‐reactive agents on 〔^3H〕glutamate binding in brain synaptic membranes treated with Triton X‐100" Neurochemistry International. 18. 55-62 (1991)

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)

大森 哲朗,小山 司,中村 文裕 王 平,山下 格: "NMDA受容体を介するDA遊離反応に及ぼす扁桃核キンドリングの影響" 神経化学. 30. 152-153 (1991)

Tetsuro Omori、Tsukasa Koyama、Fumihiro Nakamura、Ping Wang、Itaru Yamashita：“杏仁核点燃对 NMDA 受体介导的 DA 释放反应的影响”《神经化学》30. 152-153 (1991)。

Y.Tanii,T.Nishikawa,A.Hashimoto & K.Takahashi: "Stereoselective inhibition by D‐and L‐alanine of phencyclidine‐induced locomotor Stimulation in the rat" Brain Research. 563. 281-284 (1991)

Y.Tanii、T.Nishikawa、A.Hashimoto 和 K.Takahashi：“D- 和 L-丙氨酸对苯环己哌啶诱导的大鼠运动刺激的立体选择性抑制”《大脑研究》563. 281-284 (1991)。

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).

M.Ishomaru 等人：“慢性精神分裂症患者大脑皮层中马钱子碱不敏感的甘氨酸结合位点的交叉：谷氨酸假说的证据”生物精神病学。