Article ; Online: Myelination is delayed during postnatal brain development in the mdx mouse model of Duchenne muscular dystrophy.
BMC neuroscience
2017 Volume 18, Issue 1, Page(s) 63
Abstract: Background: In Duchenne muscular dystrophy (DMD), the loss of the dystrophin component of the dystrophin-glycoprotein complex (DGC) compromises plasma membrane integrity in skeletal muscle, resulting in extensive muscle degeneration. In addition, many ... ...
| Abstract | Background: In Duchenne muscular dystrophy (DMD), the loss of the dystrophin component of the dystrophin-glycoprotein complex (DGC) compromises plasma membrane integrity in skeletal muscle, resulting in extensive muscle degeneration. In addition, many DMD patients exhibit brain deficits in which the cellular etiology remains poorly understood. We recently found that dystroglycan, a receptor component of the DGC that binds intracellularly to dystrophin, regulates the development of oligodendrocytes, the myelinating glial cells of the brain. Results: We investigated whether dystrophin contributes to oligodendroglial function and brain myelination. We found that oligodendrocytes express up to three dystrophin isoforms, in conjunction with classic DGC components, which are developmentally regulated during differentiation and in response to extracellular matrix engagement. We found that mdx mice, a model of DMD lacking expression of the largest dystrophin isoform, have delayed myelination and inappropriate oligodendrocyte progenitor proliferation in the cerebral cortex. When we prevented the expression of all oligodendroglial dystrophin isoforms in cultured oligodendrocytes using RNA interference, we found that later stages of oligodendrocyte maturation were significantly delayed, similar to mdx phenotypes in the developing brain. Conclusions: We find that dystrophin is expressed in oligodendrocytes and influences developmental myelination, which provides new insight into potential cellular contributors to brain dysfunction associated with DMD. |
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| MeSH term(s) | Animals ; Brain/growth & development ; Brain/metabolism ; Brain/pathology ; Cells, Cultured ; Disease Models, Animal ; Female ; Gene Expression Regulation, Developmental ; Male ; Mice, Inbred C57BL ; Mice, Inbred mdx ; Muscular Dystrophy, Duchenne/metabolism ; Muscular Dystrophy, Duchenne/pathology ; Neural Stem Cells/metabolism ; Neural Stem Cells/pathology ; Oligodendroglia/metabolism ; Oligodendroglia/pathology ; Protein Isoforms ; RNA Interference ; RNA, Messenger/metabolism ; Rats, Sprague-Dawley |
| Chemical Substances | Protein Isoforms ; RNA, Messenger |
| Language | English |
| Publishing date | 2017-08-14 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. |
| ISSN | 1471-2202 |
| ISSN (online) | 1471-2202 |
| DOI | 10.1186/s12868-017-0381-0 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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