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Central Nervous System Involvement in the Animal Model of Myodystrophy

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Abstract

Congenital muscular dystrophies present mutated gene in the LARGE mice model and it is characterized by an abnormal glycosylation of α-dystroglycan (α-DG), strongly implicated as having a causative role in the development of central nervous system abnormalities such as cognitive impairment seen in patients. However, the pathophysiology of the brain involvement remains unclear. Therefore, the objective of this study is to evaluate the oxidative damage and energetic metabolism in the brain tissue as well as cognitive involvement in the LARGE(myd) mice model of muscular dystrophy. With this aim, we used adult homozygous, heterozygous, and wild-type mice that were divided into two groups: behavior and biochemical analyses. In summary, it was observed that homozygous mice presented impairment to the habituation and avoidance memory tasks; low levels of brain-derived neurotrophic factor (BDNF) in the prefrontal cortex, hippocampus, cortex and cerebellum; increased lipid peroxidation in the prefrontal cortex, hippocampus, striatum, and cerebellum; an increase of protein peroxidation in the prefrontal cortex, hippocampus, striatum, cerebellum, and cortex; a decrease of complex I activity in the prefrontal cortex and cerebellum; a decrease of complex II activity in the prefrontal cortex and cerebellum; a decrease of complex IV activity in the prefrontal cortex and cerebellum; an increase in the cortex; and an increase of creatine kinase activity in the striatum and cerebellum. This study shows the first evidence that abnormal glycosylation of α-DG may be affecting BDNF levels, oxidative particles, and energetic metabolism thus contributing to the memory storage and restoring process.

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Acknowledgments

This research was supported by grants from CNPq (CMC, JQ, FD-P, and ELS), FAPESC (JQ, FD-P and ELS), and UNESC (JQ, FD-P, and ELS). ELS, FDP, and JQ are CNPq research fellows. CMC is a holder of a CNPq studentship.

Conflict of interest

None of the authors or funding sources has conflict of interest.

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Authors and Affiliations

  1. Laboratory of Experimental Neurosciences, University of Southern Santa Catarina, 88137-270, Palhoca, Santa Catarina, Brazil

    Clarissa M. Comim

  2. Laboratory of Neurosciences and National Institute for Translational Medicine (INCT-TM), Health Sciences Unit, University of Southern Santa Catarina, 88806-000, Criciúma, Santa Catarina, Brazil

    Bruna P. Mendonça, Diogo Dominguini, Andreza L. Cipriano & Amanda V. Steckert

  3. Laboratory of Experimental Pathophysiology and National Institute for Translational Medicine (INCT-TM), Health Sciences Unit, University of Southern Santa Catarina, 88806-000, Criciúma, Santa Catarina, Brazil

    Giselli Scaini, Emílio L. Streck, Felipe Dal-Pizzol & João Quevedo

  4. Human Genome Research Center, Biosciences Institute, University of São Paulo, São Paulo, São Paulo, Brazil

    Mariz Vainzof

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  1. Clarissa M. Comim
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  2. Bruna P. Mendonça
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Correspondence to Clarissa M. Comim.

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Comim, C.M., Mendonça, B.P., Dominguini, D. et al. Central Nervous System Involvement in the Animal Model of Myodystrophy. Mol Neurobiol 48, 71–77 (2013). https://doi.org/10.1007/s12035-013-8415-9

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  • DOI: https://doi.org/10.1007/s12035-013-8415-9

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