New MS studies tease that exercise promotes "remarkable" remyelination, neuroprotection

[ActiveMSers]

Life Sciences

Volume 277, 15 July 2021, 119459
Neuroprotective role of galantamine with/without physical exercise in experimental autoimmune encephalomyelitis in rats

Mohamed A.El-Emam^aSamarEl Achy^bDalaal M.Abdallah^cHanan S.El-Abhar^dMennatallah A.Gowayed^a


https://doi.org/10.1016/j.lfs.2021.119459

Highlights

•Neuroprotective role of galantamine via anti-inflammatory/anti-apoptotic characters
•Galantamine attenuates EAE severity and reverses demyelination.
•Galantamine can govern the immune response in MS through its action on T-cells.
•Exercise training proves a potential therapeutic role in MS.
•Exercise training could augment the beneficial effects of galantamine.

Abstract

Aims

The fact that physical activity besides central cholinergic enhancement contributes in improving neuronal function and spastic plasticity, recommends the use of the anticholinesterase and cholinergic drug galantamine with/without exercise in the management of the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS).

Materials and methods

Sedentary and 14 days exercised male Sprague Dawley rats were subjected to EAE. Hereafter, exercised rats continued on rotarod for 30 min for 17 consecutive days. At the onset of symptoms (day 13), EAE sedentary/exercised groups were subdivided into untreated and post-treated with galantamine. The disease progression was assessed by EAE score, motor performance, and biochemically using cerebrospinal fluid (CSF). Cerebellum and brain stem samples were used for histopathology and immunohistochemistry analysis.
Key findings


Galantamine decreased EAE score of sedentary/exercised rats and enhanced their motor performance. Galantamine with/without exercise inhibited CSF levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6), and Bcl-2-associated X protein (Bax), besides caspase-3 and forkhead box P3 (Foxp3) expression in the brain stem. Contrariwise, it has elevated CSF levels of brain derived neurotrophic factor (BDNF) and B-cell lymphoma (Bcl-2) and enhanced remyelination of cerebral neurons. Noteworthy, exercise boosted the drug effect on Bcl-2 and Bax.

Significance

The neuroprotective effect of galantamine against EAE was associated with anti-inflammatory and anti-apoptotic potentials, along with increasing BDNF and remyelination. It also normalized regulatory T-cells levels in the brain stem. The impact of the add-on of exercise was markedly manifested in reducing neuronal apoptosis.

FULL STUDY: https://www.sciencedirect.com/scienc...24320521004446

[ActiveMSers]

• Published: 31 March 2021

Exercise rapidly alters proteomes in mice following spinal cord demyelination

• Brian Mark Lozinski,
• Luiz Gustavo Nogueira de Almeida,
• Claudia Silva,
• Yifei Dong,
• Dennis Brown,
• Sameeksha Chopra,
• V. Wee Yong &
• Antoine Dufour

Scientific Reports volume 11, Article number: 7239 (2021)

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.

STUDY (FREE ACCESS):
https://www.nature.com/articles/s41598-021-86593-5

[Suebee]

Mouse study, but I’ll take it.