Pathology of schizophrenia by regulation of oligodendrocyte related-genes

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09814
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Maekawa Motoko 国立研究開発法人理化学研究所, 脳科学総合研究センター, 研究員 (50435731)
• Co-Investigator(Renkei-kenkyūsha): YOSHIKAWA Takeo 国立研究開発法人理化学研究所, 脳科学総合研究センター, チームリーダー (30249958) ; OHNISHI Tetsuo 国立研究開発法人理化学研究所, 脳科学総合研究センター, 副チームリーダー (80373281) ; TOYOSHIMA Manabu 国立研究開発法人理化学研究所, 脳科学総合研究センター, 研究員 (90582750) ; SHIMAMOTO Chie 国立研究開発法人理化学研究所, 脳科学総合研究センター, 研究員 (90755117)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: オリゴデンドロサイト / RXR / 統合失調症

Outline of Final Research Achievements

We hypothesized that specific nuclear receptors regulate expressions of multiple oligodendrocyte-related genes and that they are implicated in the schizophrenia pathology. We found that RXR agonist bexarotene increased the expression levels of the oligodendrocyte-related genes and that the RXR antagonist HX531 decreased them in the OLP6 cells (the oligodendrocyte cell line). The RXR agonist bexarotene also elicited a trend toward increased expression of those genes in wild type mice. Treatment of mice with bexarotene tended to suppress the hyper-locomotive responses induced by MK-801. Notably, expressions of the nuclear receptor genes were found to be down-regulated in hair follicles cells from individuals affected with schizophrenia. Taken together, these results suggest that the RXR system regulates oligodendrocyte-related genes, thereby playing a crucial role in the schizophrenia pathophysiology.

Free Research Field

精神医学