Cuprizone short-term exposure: Astrocytic IL-6 activation and behavioral changes relevant to psychosis

NEUROBIOLOGY OF DISEASE

卷:59

Article

Tezuka, Tomoaki¹  Tamura, Makoto¹  Kondo, Mari A.²  Sakaue, Masaki¹  Okada, Kinya¹  Takemoto, Kana¹  Fukunari, Atsushi¹  Miwa, Keiko¹  Ohzeki, Hiromitsu¹  Kano, Shin-ichi²  Yasumatsu, Hiroshi¹  Sawa, Akira²  Kajii, Yasushi¹ 

[1] Mitsubishi Tanabe Pharma Corp, Yokohama, Kanagawa, Japan

[2] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA

关键词: Inflammation;    Astrocyte;    Cytokine;    Interleukin-6;    Schizophrenia;   

DOI  :  10.1016/j.nbd.2013.07.003

来源: Elsevier

【 摘 要 】

A growing body of evidence suggests the involvement of inflammatory processes in the pathophysiology of schizophrenia. Four- to 8-week exposure-to cuprizone, a copper chelator, causes robust demyelination and has been used to build a model for multiple sclerosis. In contrast, we report here the effects of 1-week cuprizone exposure in mice. This short-term cuprizone exposure elicits behavioral changes that include augmented responsiveness to methamphetamine and phencyclidine, as well as impaired working memory. The cellular effects of 1-week cuprizone exposure differ substantially from the longer-term exposure; perturbation of astrocytes and microglia is induced without any sign of demyelination. Furthermore, the proinflammatory cytokine interleukin-6 was significantly up-regulated in glial fibrillary acidic protein (GFAP)-positive cells. We propose that this cuprizone short-term exposure may offer a model to study some aspects of biology relevant to schizophrenia and related conditions. (C) 2013 Published by Elsevier Inc.

【 授权许可】

Free