Exercise rapidly alters proteomes in mice following spinal cord demyelination

Abstract

Exercise affords broad benefits for people with multiple sclerosis (PwMS) including less fatigue, depression, and improved cognition. In animal models of multiple sclerosis (MS), exercise has been shown to improve remyelination, decrease blood–brain barrier permeability and reduce leukocyte infiltration. Despite these benefits many PwMS refrain from engaging in physical activity. This barrier to participation in exercise may be overcome by uncovering and describing the mechanisms by which exercise promotes beneficial changes in the central nervous system (CNS). Here, we show that acute bouts of exercise in mice profoundly alters the proteome in demyelinating lesions. Following lysolecithin induced demyelination of the ventral spinal cord, mice were given immediate access to a running wheel for 4 days. Lesioned spinal cords and peripheral blood serum were then subjected to tandem mass tag labeling shotgun proteomics workflow to identify alteration in protein levels. We identified 86 significantly upregulated and 85 downregulated proteins in the lesioned spinal cord as well as 14 significantly upregulated and 11 downregulated proteins in the serum following acute exercise. Altered pathways following exercise in demyelinated mice include oxidative stress response, metabolism and transmission across chemical synapses. Similar acute bout of exercise in naïve mice also changed several proteins in the serum and spinal cord, including those for metabolism and anti-oxidant responses. Improving our understanding of the mechanisms and duration of activity required to influence the injured CNS should motivate PwMS and other conditions to embrace exercise as part of their therapy to manage CNS disability.

The functional mechanisms of synchronizing royal jelly consumption and physical activity on rat with multiple sclerosis-like behaviors hallmarks based on bioinformatics analysis, and experimental survey

“…revealed that the alternation of genes is related to the metabolism pathway. They indicated that the expression protein of Pgam2 in glycolysis and Ndufb9, Ndufv3, and mt-Nd3 associated with mitochondria significantly changed by exercise training [ 2 ]. In this regard, we found that physical activity improved the motor function, proinflammatory cytokine, and demyelination of the Multiple sclerosis rats.…”

“…Evidence has indicated that physical activity could modulate the brain’s structure and connectome [ 38 , 39 ]. Moreover, based on the literature review, exercise training might ameliorate fatigue, depression, neurogenesis, neuroprotection, remyelination, and cognition [ 2 , 40 , 41 ]. Lourenco and colleagues demonstrated that aerobic exercise could increase the expression level of the Nrf2 as a vital transcription factor and antioxidant enzymes activity.…”

“…Moreover, This condition affects millions of individuals worldwide, and progressive degenerative diseases can influence body activities and functions such as breathing, moving, talking, and balance. For example, multiple sclerosis (MSc) is the prevalent neurodegenerative disorder caused by increasing neuroinflammation, which stimulates the immune cells and destroys neurons, axons, and myelin-producing oligodendrocytes [ 2 ].…”

“…Evidence has indicated that physical activity in rodents with experimental autoimmune encephalomyelitis (EAE) significantly decreased demyelination in the lumbar spinal cord and immune cell infiltration [ 16 ]. In addition, exercise may consider a preventive therapy for developing the risk of the MSc [ 2 ]. Moreover, exercise can delay disease onset and preserve the motor neurons in the lumbar spinal cord and axons, which reduces the severity of disability [ 2 ].…”

“…In addition, exercise may consider a preventive therapy for developing the risk of the MSc [ 2 ]. Moreover, exercise can delay disease onset and preserve the motor neurons in the lumbar spinal cord and axons, which reduces the severity of disability [ 2 ].…”