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

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.

• Authors: 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
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 59 Pg. 63-8 (Nov 2013) ISSN: 1095-953X [Electronic] United States
• PMID: 23867234 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Central Nervous System Stimulants
• Chelating Agents
• Glial Fibrillary Acidic Protein
• Hallucinogens
• Interleukin-6
• Methamphetamine
• Cuprizone
• Copper
• Phencyclidine

Topics

• Animals
• Astrocytes (drug effects, metabolism, ultrastructure)
• Brain (drug effects, pathology, ultrastructure)
• Central Nervous System Stimulants (toxicity)
• Chelating Agents (toxicity)
• Copper (metabolism)
• Cuprizone (toxicity)
• Disease Models, Animal
• Gene Expression Regulation (drug effects)
• Glial Fibrillary Acidic Protein (genetics, metabolism)
• Hallucinogens (toxicity)
• Hyperkinesis (chemically induced)
• Interleukin-6 (genetics, metabolism)
• Male
• Methamphetamine (toxicity)
• Mice
• Mice, Inbred C57BL
• Phencyclidine (toxicity)
• Psychotic Disorders (etiology, pathology, physiopathology)
• Time Factors