Swim Training Modulates Skeletal Muscle Energy Metabolism, Oxidative Stress, and Mitochondrial Cholesterol Content in Amyotrophic Lateral Sclerosis Mice.

Damian Jozef Flis,Malgorzata Halon-Golabek,Jedrzej Antosiewicz,Mariusz Roman Wieckowski,Wieslaw Ziolkowski,Katarzyna Dzik,Jan Jacek Kaczor

doi:10.1155/2018/5940748

Abstract

Recently, in terms of amyotrophic lateral sclerosis (ALS), much attention has been paid to the cell structures formed by the mitochondria and the endoplasmic reticulum membranes (MAMs) that are involved in the regulation of Ca2+ signaling, mitochondrial bioenergetics, apoptosis, and oxidative stress. We assumed that remodeling of these structures via swim training may accompany the prolongation of the ALS lifespan. In the present study, we used transgenic mice with the G93A hmSOD1 gene mutation. We examined muscle energy metabolism, oxidative stress parameters, and markers of MAMs (Caveolin-1 protein level and cholesterol content in crude mitochondrial fraction) in groups of mice divided according to disease progression and training status. The progression of ALS was related to the lowering of Caveolin-1 protein levels and the accumulation of cholesterol in a crude mitochondrial fraction. These changes were associated with aerobic and anaerobic energy metabolism dysfunction and higher oxidative stress. Our data indicated that swim training prolonged the lifespan of ALS mice with accompanying changes in MAM components. Swim training also maintained mitochondrial function and lowered oxidative stress. These data suggest that modification of MAMs might play a crucial role in the exercise-induced deceleration of ALS development.

Highlights

Amyotrophic lateral sclerosis (ALS) is an incurable, chronic neurodegenerative disease characterized by selective death of motoneurons in the motor cortex, brainstem, and spinal cord that control any muscle action [1]
We demonstrated that the beneficial effects of forced swimming on the lifespan of ALS mice might be related to changes in skeletal muscle oxidative stress and bioenergetics
Progression of ALS is accompanied by a reduction in the Cav-1 protein level, accumulation of cholesterol in crude mitochondria, and decrease in energy metabolism in skeletal muscle

Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is an incurable, chronic neurodegenerative disease characterized by selective death of motoneurons in the motor cortex, brainstem, and spinal cord that control any muscle action [1]. It is important to note that causes of neurodegeneration in ALS occur outside of the nervous system. Overexpression of SOD1G93A in skeletal muscle initiates motoneuron death [2] and causes profound muscle atrophy [2, 3]. Analysis of the changes in muscle, especially related to skeletal muscle mitochondria, from transgenic animals can help to better understand the pathomechanism of the disease. Mitochondrial abnormalities are common in many forms of ALS and include morphological and functional aberrations, such as disruption of Ca2+

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