Some dystrophy phenotypes of dystrophin-deficient mdx mice are exacerbated by mild, repetitive daily stress.
Animals
Disease Models, Animal
Dystrophin
/ deficiency
Heart
/ physiopathology
Hypothalamo-Hypophyseal System
/ physiopathology
Mice, Inbred mdx
Mice, Transgenic
Muscle Contraction
/ physiology
Muscle, Skeletal
/ metabolism
Muscular Dystrophy, Duchenne
/ genetics
Phenotype
Pituitary-Adrenal System
/ physiopathology
Duchenne muscular dystrophy
Dystrophin
fibrosis
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:
04 2021
04 2021
Historique:
revised:
27
01
2021
received:
12
11
2020
accepted:
15
02
2021
entrez:
18
3
2021
pubmed:
19
3
2021
medline:
16
7
2021
Statut:
ppublish
Résumé
Psychosocial stressors can cause physical inactivity, cardiac damage, and hypotension-induced death in the mdx mouse model of Duchenne muscular dystrophy (DMD). Because repeated exposure to mild stress can lead to habituation in wild-type mice, we investigated the response of mdx mice to a mild, daily stress to determine whether habituation occurred. Male mdx mice were exposed to a 30-sec scruff restraint daily for 12 weeks. Scruff restraint induced immediate physical inactivity that persisted for at least 60 minutes, and this inactivity response was just as robust after 12 weeks as it was after one day. Physical inactivity in the mdx mice was not associated with acute skeletal muscle contractile dysfunction. However, skeletal muscle of mdx mice that were repeatedly stressed had slow-twitch and tetanic relaxation times and trended toward high passive stiffness, possibly due to a small but significant increase in muscle fibrosis. Elevated urinary corticosterone secretion, adrenal hypertrophy, and a larger adrenal cortex indicating chronic activation of the hypothalamic-pituitary-adrenal (HPA) axis were measured in 12-week stressed mdx mice relative to those unstressed. However, pharmacological inhibition of the HPA axis did not affect scruff-induced physical inactivity and acute corticosterone injection did not recapitulate the scruff-induced phenotype, suggesting the HPA axis is not the driver of physical inactivity. Our results indicate that the response of mdx mice to an acute mild stress is non-habituating and that when that stressor is repeated daily for weeks, it is sufficient to exacerbate some phenotypes associated with dystrophinopathy in mdx mice.
Identifiants
pubmed: 33734502
doi: 10.1096/fj.202002500R
doi:
Substances chimiques
Dystrophin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21489Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR042423
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR049899
Pays : United States
Informations de copyright
© 2021 Federation of American Societies for Experimental Biology.
Références
Ervasti JM. Costameres: the Achilles' heel of Herculean muscle. J Biol Chem. 2003;278:13591-13594.
Rybakova IN, Patel JR, Ervasti JM. The dystrophin complex forms a mechanically strong link between the sarcolemma and costameric actin. J Cell Biol. 2000;150:1209-1214.
Wynn TA, Barron L. Macrophages: master regulators of inflammation and fibrosis. Semin Liver Dis. 2010;30:245-257.
Hoffman EP, Brown RH, Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell. 1987;51:919-928.
Wicksell RK, Kihlgren M, Melin L, Eeg-Olofsson O. Specific cognitive deficits are common in children with Duchenne muscular dystrophy. Dev Med Child Neurol. 2007;46:154-159.
Chaussenot R, Edeline J-M, Le Bec B, El Massioui N, Laroche S, Vaillend C. Cognitive dysfunction in the dystrophin-deficient mouse model of Duchenne muscular dystrophy: a reappraisal from sensory to executive processes. Neurobiol Learn Mem. 2015;124:111-122.
Sekiguchi M, Zushida K, Yoshida M, et al. A deficit of brain dystrophin impairs specific amygdala GABAergic transmission and enhances defensive behaviour in mice. Brain. 2009;132:124-135.
Vaillend C, Chaussenot R. Relationships linking emotional, motor, cognitive and GABAergic dysfunctions in dystrophin-deficient mdx mice. Hum Mol Genet. 2017;26:1041-1055.
Belanto JJ, Olthoff JT, Mader TL, et al. Independent variability of microtubule perturbations associated with dystrophy in the mdx mouse. Hum Mol Genet. 2016;25:4951-4961.
Belanto JJ, Mader TL, Eckhoff MD, et al. Microtubule binding distinguishes dystrophin from utrophin. Proc Natl Acad Sci. 2014;111:5723-5728.
Razzoli M, Lindsay A, Law M, et al. Social stress is lethal in the mdx model of Duchenne Muscular Dystrophy. EBioMedicine. 2020;55:102700.
Aupy P, Zarrouki F, Sandro Q, et al. Long term efficacy of AAV9-U7snRNA mediated exon 51 skipping in Mdx52 mice. Mol Ther Methods Clin Dev; 2020;17:1037-1047.
Kobayashi YM, Rader EP, Crawford RW, et al. Sarcolemma-localized nNOS is required to maintain activity after mild exercise. Nature. 2008;456:511-515.
Yamamoto K, Yamada D, Kabuta T, Takahashi A, Wada K, Sekiguchi M. Reduction of abnormal behavioral response to brief restraint by information from other mice in dystrophin-deficient mdx mice. Neuromuscul Disord. 2010;20:505-511.
Pastoret C, Sebille A. mdx mice show progressive weakness and muscle deterioration with age. J Neurol Sci. 1995;129:97-105.
Lindsay A, Southern WM, McCourt PM, et al. Variable cytoplasmic actin expression impacts the sensitivity of different dystrophin-deficient mdx skeletal muscle to eccentric contraction. FEBS J. 2019;286:2562-2576.
Rorabaugh BR, Mabe NW, Seeley SL, et al. Myocardial fibrosis, inflammation, and altered cardiac gene expression profiles in rats exposed to a predator-based model of posttraumatic stress disorder. Stress. 2020;23:125-135.
Moran AL, Warren GL, Lowe DA. Soleus and EDL muscle contractility across the lifespan of female C57BL/6 mice. Exp Gerontol. 2005;40:966-975.
Lindsay A, Baumann CW, Rebbeck RT, et al. Mechanical factors tune the sensitivity of mdx muscle to eccentric strength loss and its protection by antioxidant and calcium modulators. Skelet Muscle. 2020;10:3.
Nelson DM, Lindsay A, Judge LM, et al. Variable rescue of microtubule and physiological phenotypes in mdx muscle expressing different miniaturized dystrophins. Hum Mol Genet. 2018;27:2090-2100.
Lindsay A, Janmale T, Draper N, Gieseg SP. Measurement of changes in urinary neopterin and total neopterin in body builders using SCX HPLC. Pteridines. 2014;25:53-63.
Woessner JF. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch Biochem Biophys. 1961;93:440-447.
Strakova J, Kamdar F, Kulhanek D, et al. Integrative effects of dystrophin loss on metabolic function of the mdx mouse. Sci Rep. 2018;8:13624.
Thompson RF, Spencer WA. Habituation: a model phenomenon for the study of neuronal substrates of behavior. Psychol Rev. 1966;73:16-43.
Grissom N, Bhatnagar S. Habituation to repeated stress: get used to it. Neurobiol Learn Mem. 2009;92:215-224.
Swiderski K, Todorov M, Gehrig SM, et al. Tranilast administration reduces fibrosis and improves fatigue resistance in muscles of mdx dystrophic mice. Fibrogenesis Tissue Repair. 2014;7:1.
Harper SQ, Hauser MA, DelloRusso C, et al. Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy. Nat Med. 2002;8:253-261.
Phelps SF, Hauser MA, Cole NM, et al. Expression of full-length and truncated dystrophin mini-genes in transgenic mdx mice. Hum Mol Genet. 1995;4:1251-1258.
Miller GE, Cohen S, Ritchey AK. Chronic psychological stress and the regulation of pro-inflammatory cytokines: a glucocorticoid-resistance model. Heal Psychol. 2002;21:531-541.
Bonnefont-Rousselot D, Mahmoudi A, Mougenot N, et al. Catecholamine effects on cardiac remodelling, oxidative stress and fibrosis in experimental heart failure. Redox Rep. 2002;7:145-151.
Salaria S, Chana G, Caldara F, et al. Microarray analysis of cultured human brain aggregates following cortisol exposure: implications for cellular functions relevant to mood disorders. Neurobiol Dis. 2006;23:630-636.
Smith ELP, Batuman OA, Trost RC, Coplan JD, Rosenblum LA. Transforming growth factor-β1 and cortisol in differentially reared primates. Brain Behav Immun. 2002;16:140-149.
Johansen IB, Lunde IG, Røsjø H, et al. Cortisol response to stress is associated with myocardial remodeling in salmonid fishes. J Exp Biol. 2011;214:1313-1321.
Quinlan JG, Hahn HS, Wong BL, Lorenz JN, Wenisch AS, Levin LS. Evolution of the mdx mouse cardiomyopathy: physiological and morphological findings. Neuromuscul Disord. 2004;14:491-496.
Stedman HH, Sweeney HL, Shrager JB, et al. The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy. Nature. 1991;352:536-539.
Koolhaas JM, Bartolomucci A, Buwalda B, et al. Stress revisited: a critical evaluation of the stress concept. Neurosci Biobehav Rev. 2011;35:1291-1301.