Sensitivity to behavioral stress impacts disease pathogenesis in dystrophin-deficient mice.
blood pressure
dystrophin
estrogen
hypothalamic pituitary adrenal axis
skeletal muscle
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
21
10
2021
received:
15
07
2021
accepted:
25
10
2021
entrez:
15
11
2021
pubmed:
16
11
2021
medline:
21
12
2021
Statut:
ppublish
Résumé
Mutation to the gene encoding dystrophin can cause Duchenne muscular dystrophy (DMD) and increase the sensitivity to stress in vertebrate species, including the mdx mouse model of DMD. Behavioral stressors can exacerbate some dystrophinopathy phenotypes of mdx skeletal muscle and cause hypotension-induced death. However, we have discovered that a subpopulation of mdx mice present with a wildtype-like response to mild (forced downhill treadmill exercise) and moderate (scruff restraint) behavioral stressors. These "stress-resistant" mdx mice are more physically active, capable of super-activating the hypothalamic-pituitary-adrenal and renin-angiotensin-aldosterone pathways following behavioral stress and they express greater levels of mineralocorticoid and glucocorticoid receptors in striated muscle relative to "stress-sensitive" mdx mice. Stress-resistant mdx mice also presented with a less severe striated muscle histopathology and greater exercise and skeletal muscle oxidative capacity at rest. Most interestingly, female mdx mice were more physically active following behavioral stressors compared to male mdx mice; a response abolished after ovariectomy and rescued with estradiol. We demonstrate that the response to behavioral stress greatly impacts disease severity in mdx mice suggesting the management of stress in patients with DMD be considered as a therapeutic approach to ameliorate disease progression.
Identifiants
pubmed: 34780665
doi: 10.1096/fj.202101163RR
doi:
Substances chimiques
Dmd protein, mouse
0
Dystrophin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e22034Informations de copyright
© 2021 Federation of American Societies for Experimental Biology.
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