Physical exercise modulates T cell activity and mitigates synaptic dysfunction in multiple sclerosis through vagus...

Area of Science:

• Neuroimmunology
• Exercise Physiology
• Metabolic Research

Background:

• Physical exercise (PE) shows promise for multiple sclerosis (MS), potentially mitigating immune dysregulation and inflammation-driven synaptotoxicity.
• Mechanisms underlying PE's benefits in MS, particularly its impact on T cell immunometabolism and neuroinflammation, require further elucidation.

Purpose of the Study:

• To investigate the effects of PE on T cell immunometabolic function and synaptotoxicity in experimental autoimmune encephalomyelitis (EAE) mice and progressive MS (PMS) patients.
• To assess the role of vagal innervation in mediating PE's effects in the EAE model.

Main Methods:

• Utilized EAE mouse models and PMS subjects, employing cervical vagotomy in mice to assess vagal nerve contribution.
• Analyzed T cell proliferation, activation, and metabolic activity, alongside mitochondrial respiration and patch-clamp recordings for synaptotoxicity assessment.

Main Results:

• PE improved EAE clinical outcomes, reduced neuronal damage, and modulated T cell activity; effects were partially reduced by vagotomy.
• In PMS subjects, PE enhanced clinical outcomes, boosted T cell mitochondrial respiration, and abolished T cell-mediated glutamatergic synaptotoxicity.

Conclusions:

• Physical exercise demonstrates disease-modifying potential in MS by enhancing T cell function and reducing synaptotoxicity.
• The vagal pathway is identified as a crucial mediator of exercise-induced neuroimmune benefits in MS.