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Clemastine rescues behavioral changes and enhances remyelination in the cuprizone mouse model of demyelination

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Abstract

Increasing evidence suggests that white matter disorders based on myelin sheath impairment may underlie the neuropathological changes in schizophrenia. But it is unknown whether enhancing remyelination is a beneficial approach to schizophrenia. To investigate this hypothesis, we used clemastine, an FDA-approved drug with high potency in promoting oligodendroglial differentiation and myelination, on a cuprizone-induced mouse model of demyelination. The mice exposed to cuprizone (0.2% in chow) for 6 weeks displayed schizophrenia-like behavioral changes, including decreased exploration of the center in the open field test and increased entries into the arms of the Y-maze, as well as evident demyelination in the cortex and corpus callosum. Clemastine treatment was initiated upon cuprizone withdrawal at 10 mg/kg per day for 3 weeks. As expected, myelin repair was greatly enhanced in the demyelinated regions with increased mature oligodendrocytes (APC-positive) and myelin basic protein. More importantly, the clemastine treatment rescued the schizophrenia-like behavioral changes in the open field test and the Y-maze compared to vehicle, suggesting a beneficial effect via promoting myelin repair. Our findings indicate that enhancing remyelination may be a potential therapy for schizophrenia.

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Authors and Affiliations

  1. Department of Neurology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, 100071, China

    Zhifang Li, Shuangyi Fan & Binbin Sun

  2. Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400038, China

    Yangtao He

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  1. Zhifang Li
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  2. Yangtao He
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  4. Binbin Sun
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Correspondence to Zhifang Li or Yangtao He.

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These authors contributed equally to this work.

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Li, Z., He, Y., Fan, S. et al. Clemastine rescues behavioral changes and enhances remyelination in the cuprizone mouse model of demyelination. Neurosci. Bull. 31, 617–625 (2015). https://doi.org/10.1007/s12264-015-1555-3

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  • DOI: https://doi.org/10.1007/s12264-015-1555-3

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