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Cuprizone-induced demyelination in mice: age-related vulner-ability and exploratory behavior deficit

Neuroscience Bulletin 2013年第2期29卷 251-259页

作者： Hongkai Wang Chengren Li Hanzhi Wang Feng Mei Zhi Liu Hai-Ying Shen Lan Xiao Department of Histology and Embryology Chongqing Key Laboratory of NeurobiologyThird Military Medical University Robert Stone Dow Neurobiology Laboratories Legacy Research Institute

Schizophrenia is a mental disease that mainly affects young individuals （15 to 35 years old） but its etiology remains largely undefined. Recently, accumulating evidence indicated that demyelination and/or dysfunction of oligodendrocytes is an important feature of its pathogenesis. We hypothesized that the vulnerability of young individuals to demyelination may contribute to the onset of schizophrenia. In the present study, three different age cohorts of mice, i.e. juvenile （3 weeks）, young-adult （6 weeks） and middle-aged （8 months）, were subjected to a 6-week diet containing 0.2% cuprizone （CPZ） to create an animal model of acute demyelination. Then, age-related vulnerability to CPZ-induced demyelination, behavioral outcomes, and myelination-related molecular biological changes were assessed. We demonstrated：（1） CPZ treatment led to more severe demyelination in juvenile and young-adult mice than in middle-aged mice in the corpus callosum, a region closely associated with the pathophysiology of schizophrenia; （2） the higher levels of demyelination in juvenile and young-adult mice were correlated with a greater reduction of myelin basic protein, more loss of CC-1- positive mature oligodendrocytes, and higher levels of astrocyte activation; and （3） CPZ treatment resulted in a more prominent exploratory behavior deficit in juvenile and young-adult mice than in middle-aged mice. Together, our data demonstrate an age-relatedvulnerability to demyelination with a concurrent behavioral deficit, providing supporting evidence for better understanding the susceptibility of the young to the onset of schizophrenia.

关键词： schizophrenia oligodendrocytes agedemyelination cuprizone

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