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

Academic Article

Abstract

  • 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.

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    Keywords

  • Astrocyte, Cytokine, Inflammation, Interleukin-6, Schizophrenia, Animals, Astrocytes, Brain, Central Nervous System Stimulants, Chelating Agents, Copper, Cuprizone, Disease Models, Animal, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Hallucinogens, Hyperkinesis, Interleukin-6, Male, Methamphetamine, Mice, Mice, Inbred C57BL, Phencyclidine, Psychotic Disorders, Time Factors

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    Author List

  • Tezuka T; Tamura M; Kondo MA; Sakaue M; Okada K; Takemoto K; Fukunari A; Miwa K; Ohzeki H; Kano S-I

    • Start Page

  • 63

    • End Page

  • 68

    • Volume

  • 59