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

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。

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.