Pregnancy-induced amelioration of muscular dystrophy phenotype in mdx mice via muscle membrane stabilization effect of glucocorticoid

PloS One
Yuko Shimizu-MotohashiAtsushi Asakura

Abstract

Duchenne muscular dystrophy (DMD), the most common and severe type of dystrophinopathy, is an X-linked recessive genetic disease caused by the absence of dystrophin, which leads to fragility and vulnerability of the sarcolemma to mechanical stretching with increased membrane permeability. Currently, glucocorticoids such as prednisolone are the only medication available for DMD. However, molecular pathways responsible for this effect are still unclear. In addition, it remains unclear whether sex-related factors, including pregnancy and the postpartum period, affect the phenotype of dystrophinopathy. Here, we report the amelioration of muscle membrane permeability in the diaphragm muscle of pregnant and postpartum, but not in nulliparous, mdx mice, an animal model for DMD, during the physiological surge of corticosterone, the most abundant glucocorticoid in rodents. Cultures of single muscle fibers and myotubes isolated from mdx mouse diaphragm demonstrate resistance to hypo-osmotic shock when treated with corticosterone but not with estradiol or progesterone. This corticosterone-mediated resistance was diminished by an antagonist of corticosterone, indicating that the glucocorticoid-glucocorticoid receptor axis plays a role in t...Continue Reading

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Citations

Oct 18, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Feng YueShihuan Kuang
May 20, 2021·The Journal of Cell Biology·Nobuko Katoku-KikyoNobuaki Kikyo
Nov 16, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Angus LindsayAaron P Russell

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Methods Mentioned

BETA
PCR
Protein Assay
electrophoresis
fluorescence microscopy

Software Mentioned

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