A study of molecular pathogenesis of anxiety disorders in the brain.

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15591212
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: TOKYO MEDICAL AND DENTAL UNIVERSITY
• Principal Investigator: KURUMAJI Akeo TOKYO MEDICAL & DENTAL UNIVESITY, SCHOOL OF MEDICINE, LECTURER, 医学部・附属病院, 講師 (00251504)
• Co-Investigator(Kenkyū-buntansha): NISHIKAWA Toru TOKYO MEDICAL & DENTAL UNIVESITY, GRADUATE SCHOOL, PROFESSOR, 大学院・医歯学総合研究科, 教授 (00198441) ; KASHIWA Atsushi TOKYO MEDICAL & DENTAL UNIVESITY, GRADUATE SCHOOL, ASSISTANT, 大学院・医歯学総合研究科, 助手 (10301227)
• Project Period (FY): 2003 – 2004
• Keywords: ANXIETY DISORDERS / ANXIOGENIC DRUG / IMMOBILIZATION STRESS / POSTNATAL DEVELOPMENT / MICROARRAY / CEREBRAL NEOCORTEX / RT-PCR / BENZODIAZEPINE RECEPTOR

Research Abstract

We examined effects of FG 7142, a partial benzodiazepine inverse agonist possessing an anxiogenic effect, on gene expressions in the cerebral cortex of mice. The total RNAs were used in the experiment of the cDNA microarray for screening the gene expression, and candidate genes involved in the response to the drug were then measured using a quantitative RT-PCR method. In addition, effects of immobilization stress and yohimbine were similarly investigated in the cortex.
The levels of mRNAs of BTG2 and CCN1 in the cerebral cortex of young adult mice were significantly increased after treatment with FG7142, yohimbine and immobilization stress. A marked increase in mRNAs of Adamts1 was observed in the cortex after FG7142 and the stress. The increases in mRNAs of the three genes (BTG2, CCN1 and Adamts1) after FG7142 were completely reversed by treatment with flumazenil (an antagonist of benzodiazepine receptor). However, in the cerebral cortex of infant mice, the injection of FG7142 produced a small increase (+ 20 %) in the gene expressions of the three genes, compared to those of the young adult mice (+ 200〜400 %).
Consequently, the present study indicates that the three genes play an important role in a stress-responsive molecular system in the brain which may be organized during the postnatal brain development.