Mild Aerobic Exercise Training Hardly Affects the Diaphragm of mdx Mice

Abstract

In the mdx mice model of Duchenne Muscular Dystrophy (DMD), mild endurance exercise training positively affected limb skeletal muscles, whereas few and controversial data exist on the effects of training on the diaphragm. The diaphragm was examined in mdx (C57BL/10ScSn-Dmdmdx) and wild-type (WT, C57BL/10ScSc) mice under sedentary conditions (mdx-SD, WT-SD) and during mild exercise training (mdx-EX, WT-EX). At baseline, and after 30 and 45 days (training: 5 d/wk for 6 weeks), diaphragm muscle morphology and Cx39 protein were assessed. In addition, tissue levels of the chaperonins Hsp60 and Hsp70 and the p65 subunit of nuclear factor-kB (NF-kB) were measured in diaphragm, gastrocnemius, and quadriceps in each experimental group at all time points. Although morphological analysis showed unchanged total area of necrosis/regeneration in the diaphragm after training, there was a trend for larger areas of regeneration than necrosis in the diaphragm of mdx-EX compared to mdx-SD mice. However, the levels of Cx39, a protein associated with active regeneration in damaged muscle, were similar in the diaphragm of mdx-EX and mdx-SD mice. Hsp60 significantly decreased at 45 days in the diaphragm, but not in limb muscles, in both trained and sedentary mdx compared to WT mice. In limb muscles, but not in the diaphragm, Hsp70 and NF-kB p65 levels were increased in mdx mice irrespective of training at 30 and 45 days. Therefore, the diaphragm of mdx mice showed little inflammatory and stress responses over time, and appeared hardly affected by mild endurance training. J. Cell. Physiol. 232: 2044-2052, 2017. © 2016 Wiley Periodicals, Inc.

Heat shock protein (Hsp) regulation by muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus

“…In the brain, Hsp60 is expressed in astrocytes, neurons, microglia, oligodendrocytes, and ependymal cells (D'Souza & Brown, ), suggesting an active participation of this chaperonin in many functions of the brain both in normal and pathological conditions. Hsp60 is a mitochondrial protein constitutively expressed under normal conditions and induced by different types of stressors such as heat shock, oxidative stress, and DNA damage (Bukau & Horwich, ; Morici et al, , ; Parnas et al, ). Inside mitochondria, Hsp60 controls the correct folding of other mitochondrial proteins and mutations of Hsp60 cause cell death secondary to severe mitochondrial protein folding defects (Bross, Magnoni, & Bie, ).…”

Skeletal Muscle Metabolism in Duchenne and Becker Muscular Dystrophy—Implications for Therapies

“…Multiple studies have examined the phenotypic outcomes of mdx mice that have been subjected to exercise (reviewed in [ 89 ]). Low-intensity endurance exercise on a motorized Rota-Rod for 6 weeks, decreased the cell degeneration, inflammation, and necrosis in limb muscles [ 147 ].…”

“…Low-intensity endurance exercise on a motorized Rota-Rod for 6 weeks, decreased the cell degeneration, inflammation, and necrosis in limb muscles [ 147 ]. Importantly, the diaphragms of the exercised mdx mice had increased regenerative areas and decreased necrosis assessed by histology, compared to sedentary mdx [ 89 ]. Voluntary wheel running also increased the mass and force of skeletal muscles [ 104 , 148 , 149 ].…”

Hsp60 in Skeletal Muscle Fiber Biogenesis and Homeostasis: From Physical Exercise to Skeletal Muscle Pathology

“…The diseases correlating with Hsp60 levels and structural impairment may have a direct effect on skeletal muscle homeostasis, or affect the central nervous system, and in turn, muscle activity (Table 1). Hsp60 levels decreased in the diaphragm muscle, but not in the quadriceps and gastrocnemius muscles of dystrophic-trained mice, suggesting the exhaustion of potentially protective mechanisms in the diaphragm [106]. Moreover, Hsp60 content was significantly higher in the extensor digitorum longus muscle of heat-stressed diabetic rats than in non-stressed diabetic rats, and its levels were similar to normal rat skeletal muscle [107].…”