1998 Fiscal Year Final Research Report Summary

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

Research Project

Project/Area Number	09670976
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Psychiatric science
Research Institution	Chiba University
Principal Investigator	KODAMA Kazuhiro Psychiatry, Associate Professor, 医学部, 助教授 (90161942)
Co-Investigator(Kenkyū-buntansha)	SHIRASAWA Hiroshi Microbiology I,Professor, 医学部, 教授 (00216194)
Project Period (FY)	1997 – 1998
Keywords	PCP / Schizophrenia / glutamate dehydrogenase
Research Abstract	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.