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Lookup NU author(s): Emine Bagdatlioglu, Dr Paola Porcari, Liz Greally, Professor Andrew BlamireORCiD, Professor Volker StraubORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2020 The AuthorsDuchenne muscular dystrophy (DMD) is an X-linked recessive muscle wasting disease caused by mutations in the DMD gene, which encodes the large cytoskeletal protein dystrophin. Approximately one-third of DMD patient's exhibit cognitive problems yet it is unknown if cognitive impairments worsen with age. The mdx mouse model is deficient in dystrophin demonstrates cognitive abnormalities, but no studies have investigated this longitudinally. We assessed the consequences of dystrophin deficiency on brain morphology and cognition in male mdx mice. We utilised non-invasive methods to monitor CNS pathology with an aim to identify changes longitudinally (between 4 and 18 months old) which could be used as outcome measures. MRI identified a total brain volume (TBV) increase in control mice with ageing (p < 0.05); but the mdx mice TBV increased significantly more (p < 0.01). Voxel-based morphometry (VBM) identified decreases in grey matter volume, particularly in the hippocampus of the mdx brain, most noticeable from 12 months onwards, as were enlarged lateral ventricles in mdx mice. The caudate putamen of older mdx mice showed increases in T2- relaxometry which may be considered as evidence of increased water content. Hippocampal spatial learning and memory was decreased in mdx mice, particularly long-term memory, which progressively worsened with age. The novel object recognition (NOR) task highlighted elevated anxiety-related behaviour in older mdx mice. Our studies suggest that dystrophin deficiency causes a progressive cognitive impairment in mice (compared to ageing control mice), becoming evident at late disease stages, and may explain why progressive CNS symptoms are not obvious in DMD patients.
Author(s): Bagdatlioglu E, Porcari P, Greally E, Blamire AM, Straub VW
Publication type: Article
Publication status: Published
Journal: Neuromuscular Disorders
Year: 2020
Volume: 30
Issue: 5
Pages: 368-388
Print publication date: 01/05/2020
Online publication date: 03/03/2020
Acceptance date: 25/02/2020
Date deposited: 23/07/2020
ISSN (print): 0960-8966
ISSN (electronic): 1873-2364
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.nmd.2020.02.018
DOI: 10.1016/j.nmd.2020.02.018
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