PCP(フェンシクリジン)投与により発現誘導される遺伝子cDNAのクローニング

通过PCP（苯环己哌啶）给药诱导表达的基因cDNA的克隆

• 批准号: 09670976
• 负责人: KODAMA Kazuhiro
• 金额: $ 0.9万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670976/
• 关键词: PCP; Schizophrenia; glutamate dehydrogenase; glutauate dehydrogenase; glutawate dehydrogenase

To clarify the molecular mechanism of phencyclidine (PCP) -induced schizophreniform psychosis in humans and behavioral abnormalities in ex-perimental animals, we used differential screening of a cDNA library from rat cerebral cortex treated with PCP.We identified a PCP-induced cDNA clone as the gene coding glutamate dehydrogenase (GDH), an enzyme central to glutamate metabolism. GDH mRNA levels significantly increased as imrnediate-early as 15 min following PCP administration in both cerebral cortex and cerebellum. This effect was observed even in the presence of protein synthesis inhibitor, cycloheximide (CHX). In contrast to a transient increase of c-fos expression, the elevation of GDH mRNA level lasted long up to 8 days after PCP injection. These results suggest that GDH mRNA induction may be involved in the pathology of PCP-induced psychosis, and that GDH can be one of the candidate genes which are vulnerable in subjects with schizophrenia.

为了阐明苯环利定（phencyclidine， PCP）诱导人类精神分裂样精神病和实验动物行为异常的分子机制，我们对PCP处理的大鼠大脑皮层cDNA文库进行了差异筛选。我们鉴定了一个pcp诱导的cDNA克隆作为谷氨酸脱氢酶（GDH）的基因编码，谷氨酸脱氢酶是谷氨酸代谢的中心酶。PCP给药后15分钟，脑皮质和小脑GDH mRNA水平均显著升高。即使在蛋白质合成抑制剂环己亚胺（CHX）存在的情况下，也观察到这种效应。与c-fos表达的短暂升高相反，PCP注射后GDH mRNA水平的升高持续时间长达8天。这些结果提示GDH mRNA的诱导可能参与了pcp诱导的精神病的病理过程，GDH可能是精神分裂症患者的候选易感基因之一。

项目成果

Shimizu et al.: "Gultamate dehydrogenase mRNA is immediately induced after phencyclidine treatment in the rat brain." Schizophr.Res.25. 251-258 (1997)

Shimizu 等人：“在大鼠大脑中接受苯环己哌啶治疗后，谷氨酸脱氢酶 mRNA 立即被诱导。”

Shimizu et al: "Expression,regulation and polymorphism of the mxil genes." Gene. 176. 45-48 (1996)

Shimizu 等人：“mxil 基因的表达、调控和多态性”。

Shimizu et al: "Gulamate dehydrogenase mRNA is immediately induced after phencyclione treatment in the rat brain." Schizophr.Res.25. 251-258 (1997)

Shimizu 等人：“在大鼠大脑中使用苯环酮处理后，古拉酸脱氢酶 mRNA 立即被诱导。”

Shimizu, E., Shirasawa, H., Kodama, K., Kuroyanagi, H., Shirasawa, T., Sato, T.and Shimizu, B: "Glutamate dehydrogenase mRNA is immediately induced after phencyclidine treatment in the rat brain." Schizophr.Res.25. 251-258 (1997)

Shimizu, E.、Shirasawa, H.、Kodama, K.、Kuroyanagi, H.、Shirasawa, T.、Sato, T. 和 Shimizu, B：“在大鼠大脑中进行苯环己哌啶治疗后，立即诱导谷氨酸脱氢酶 mRNA。”

Shimizu et al: "Expression,regulation and polymorphism of the mxi1 genes." Gene.176. 45-48 (1996)

Shimizu 等人：“mxi1 基因的表达、调控和多态性”。