J Biomed Transl Res.  2020 Dec;21(4):143-151. 10.12729/jbtr.2020.21.4.143.

Molecular factors related to skeletal muscle atrophy in a mouse model of amyotrophic lateral sclerosis

• Cai M
• Yang EJ

• KMID: 2510279
• DOI: http://doi.org/10.12729/jbtr.2020.21.4.143

Abstract

Amyotrophic lateral sclerosis (ALS) is progressive neurological disease that results in the death of motor neurons in the brain and spinal cord, leading to a decrease in skeletal muscle size and muscle weakness, wasting, or paralysis. Most research on ALS has focused on motor neuron death, and the underlying mechanisms are not well understood. This study examined the molecular mechanisms underlying muscle degeneration. We compared the protein and cytokine profiles of gastrocnemius muscle in ALS model hSOD1 ^G93A mice at pre-symptomatic and symptomatic stages by western blotting. Pro-inflammatory factors including tumor necrosis factor-α, interleukin (IL)-1β and IL-6, and cluster of differentiation 11b were upregulated in the muscle of symptomatic as compared to pre-symptomatic mice. Additionally, the levels of oxidative stress-related proteins, heme oxygenase-1 and ferritin, were increased in muscle from symptomatic as compared to pre-symptomatic mice. We also observed increased autophagy dysfunction and metabolic dysregulation in the muscles of symptomatic hSOD1 ^G93A as compared to non-Tg and pre-symptomatic hSOD1 ^G93A mice, which was accompanied by upregulation of thrombospondin-1, Prospero-related homeobox 1, glial fibrillary acidic protein, and DNA-damage-inducible 45α. Increased inflammation, oxidative stress, and autophagy contribute to motor neuron death and muscle atrophy in ALS, and the factors involved in these processes are potential therapeutic targets for treatment of this disease.

Keyword

amyotrophic lateral sclerosis; gastrocnemius muscle; hSOD1 ^G93A mice; inflammation; muscle atrophy