Cognitive dysfunction in Duchenne muscular dystrophy: a possible role for neuromodulatory immune molecules

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Rae, Mark G.
O'Malley, Dervla
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American Physiological Society
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Duchenne muscular dystrophy (DMD) is an X chromosome-linked disease characterized by progressive physical disability, immobility, and premature death in affected boys. Underlying the devastating symptoms of DMD is the loss of dystrophin, a structural protein that connects the extracellular matrix to the cell cytoskeleton and provides protection against contraction-induced damage in muscle cells, leading to chronic peripheral inflammation. However, dystrophin is also expressed in neurons within specific brain regions, including the hippocampus, a structure associated with learning and memory formation. Linked to this, a subset of boys with DMD exhibit nonprogressing cognitive dysfunction, with deficits in verbal, short-term, and working memory. Furthermore, in the genetically comparable dystrophin-deficient mdx mouse model of DMD, some, but not all, types of learning and memory are deficient, and specific deficits in synaptogenesis and channel clustering at synapses has been noted. Little consideration has been devoted to the cognitive deficits associated with DMD compared with the research conducted into the peripheral effects of dystrophin deficiency. Therefore, this review focuses on what is known about the role of full-length dystrophin (Dp427) in hippocampal neurons. The importance of dystrophin in learning and memory is assessed, and the potential importance that inflammatory mediators, which are chronically elevated in dystrophinopathies, may have on hippocampal function is also evaluated.
Duchenne muscular dystrophy , Dystrophin , Hippocampus , Learning , Memory
Rae, M.G. and O'Malley, D. (2016) 'Cognitive dysfunction in Duchenne muscular dystrophy: a possible role for neuromodulatory immune molecules', Journal of Neurophysiology, 116(3), pp.1304-1315. doi: 10.1152/jn.00248.2016
© 2016, The American Physiological Society.