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

Tomoaki Tezuka, Makoto Tamura, Mari A. Kondo, Masaki Sakaue, Kinya Okada, Kana Takemoto, Atsushi Fukunari, Keiko Miwa, Hiromitsu Ohzeki, Shin ichi Kano, Hiroshi Yasumatsu, Akira Sawa, Yasushi Kajii

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)63-68
Number of pages6
JournalNeurobiology of Disease
StatePublished - Nov 2013


  • Astrocyte
  • Cytokine
  • Inflammation
  • Interleukin-6
  • Schizophrenia

ASJC Scopus subject areas

  • Neurology


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