title: 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.affiliation: Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Tezuka
authors.forename: Makoto
authors.initials: M
authors.lastname: Tamura
authors.forename: Mari A
authors.initials: MA
authors.lastname: Kondo
authors.forename: Masaki
authors.initials: M
authors.lastname: Sakaue
authors.forename: Kinya
authors.initials: K
authors.lastname: Okada
authors.forename: Kana
authors.initials: K
authors.lastname: Takemoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukunari
authors.forename: Keiko
authors.initials: K
authors.lastname: Miwa
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Ohzeki
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Kano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yasumatsu
authors.forename: Akira
authors.initials: A
authors.lastname: Sawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kajii
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D000697:Central Nervous System Stimulants / Q000633:toxicity; D002614:Chelating Agents / Q000633:toxicity*; D003300:Copper / Q000378:metabolism; D003471:Cuprizone / Q000633:toxicity*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006213:Hallucinogens / Q000633:toxicity; D006948:Hyperkinesis / Q000139:chemically induced; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D010622:Phencyclidine / Q000633:toxicity; D011618:Psychotic Disorders / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D000697:Central Nervous System Stimulants; D002614:Chelating Agents; D005904:Glial Fibrillary Acidic Protein; D006213:Hallucinogens; D015850:Interleukin-6; D008694:Methamphetamine; D003471:Cuprizone; D003300:Copper; D010622:Phencyclidine
keywords: Astrocyte; Cytokine; Inflammation; Interleukin-6; Schizophrenia