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Increased Density of Dystrophin Protein in the Lateral Versus the Vermal Mouse Cerebellum

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Abstract

Dystrophin, present in muscle, also resides in the brain, including cerebellar Purkinje neurons. The cerebellum, although historically associated with motor abilities, is also implicated in cognition. An absence of brain dystrophin in Duchenne muscular dystrophy (DMD) and in the mdx mouse model results in cognitive impairments. Localization studies of cerebellar dystrophin, however, have focused on the vermal cerebellum, associated with motor function, and have not investigated dystrophin distribution in the lateral cerebellum, considered to mediate cognitive function. The present study examined dystrophin localization in vermal and lateral cerebellar regions and across subcellular areas of Purkinje neurons in the mouse using immunohistochemistry. In both vermal and lateral cerebellum, dystrophin was restricted to puncta on somatic and dendritic membranes of Purkinje neurons. The density of dystrophin puncta was greater in the lateral than the vermal region. Neither the size of puncta nor the area of Purkinje neuron somata differed between regions. Results support the view that cognitive deficits in the DMD and the mdx model may be mediated by the loss of dystrophin, particularly in the lateral cerebellum. Findings have important implications for future studies examining the neurophysiological sequelae of neuronal dystrophin deficiency and the role of the lateral cerebellum in cognition.

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Acknowledgments

This research was supported by an operating Grant from Manitoba Institute for Child Health (JEA and MF) and a Postgraduate Scholarship from the Natural Sciences and Engineering Research Council (WMS). The funders did not contribute to the study design, interpretation, or manuscript preparation. The authors wish to thank Ms. R. Upadhaya and Dr. W. Mizunoya (Kyushu University) for advice with cryosectioning and immunostaining and Dr. James Hare for assistance with the statistical analysis.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Psychology, University of Manitoba, P404 Duff Roblin Building, 190 Dysart Road, Winnipeg, MB, R3T 2N2, Canada

    Wanda M. Snow, Mark Fry & Judy E. Anderson

  2. Department of Biological Sciences, Faculty of Science, University of Manitoba, Biological Sciences Building, 50 Sifton Road, Winnipeg, MB, R3T 2N2, Canada

    Mark Fry & Judy E. Anderson

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  1. Wanda M. Snow
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Correspondence to Judy E. Anderson.

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Snow, W.M., Fry, M. & Anderson, J.E. Increased Density of Dystrophin Protein in the Lateral Versus the Vermal Mouse Cerebellum. Cell Mol Neurobiol 33, 513–520 (2013). https://doi.org/10.1007/s10571-013-9917-8

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