Summary: In a Multiple Sclerosis Society-funded study, researchers demonstrate that exercise enhances the rate of repair or remyelination following the development of MS-like lesions in mice. Furthermore, they identify a potential mechanism through which this repair occurs and discover that exercise combined with a drug treatment further enhances remyelination.
Background: Fatigue is a prominent symptom in multiple sclerosis (MS), hence, historically, individuals living with MS were advised to avoid physical exertion for fear that physical activity would make them feel worse. In more recent years, evidence supporting benefits of exercise in MS has emerged and healthcare practitioners are advising their patients to stay active as it is associated with reduced relapse rate, brain lesion volume, and disability progression in MS.
While research has emerged on the benefits of exercise in MS, it remains unknown if exercise is involved in mechanisms of repair. In MS, the loss of myelin, the protective covering over nerve fibers, prevents accurate transmission of signals from the brain to the body, therefore it is essential to identify mechanisms that are involved in repairing this damage. Oligodendrocytes are cells involved in the repair process by making and maintaining myelin and are found in the brain and spinal cord.
A study funded by MS Society of Canada, Alberta Innovates: Health Solutions, and Canadian Institutes of Health Research, led by researchers Samuel K. Jensen and Dr. V. Wee Yong, explores if staying active enhances the repair or remyelination in mice induced with MS-like lesions. This work was recently published in Cell Reports.
The Study: After inducing MS lesions, mice were either allowed access to an open running wheel, meaning they were allowed to run, or a locked running wheel, meaning the wheel was present but it would not move. The researchers examined if there were any changes in the repair capacity of oligodendrocytes in mice that had access to an open versus locked running wheel. Furthermore, using a method that identifies the genetic profile within a lesion, the researchers identified mechanisms underlying repair following exercise. Finally, whether a combinational approach of exercise and treatment with a drug, clemastine fumarate (an experimental drug in phase II clinical trial), further enhances remyelination was investigated.
The Results: Exercise following MS-lesions enhances the number of oligodendrocytes and rate of remyelination. This repair activates a molecule, called PGC1a, which is required for the increased rate of myelination by exercise. Finally, the combined treatment of exercising mice and clemastine fumarate was shown to further enhance remyelination demonstrating that a synergistic approach produces additive effects.
Comment: The goals of exercise in people living with MS are to improve aerobic endurance, muscular strength and endurance, flexibility, mobility, and to prevent secondary diseases such as cardiovascular disease or diabetes. There is now evidence in animals to suggest that exercise also improves the remyelination capacity in demyelinating lesions. However, it is unknown the level of activity that is needed to promote repair as mice were given free access to the running wheel. Additional research will need to be performed to investigate the type, duration, and intensity of physical exercise that is optimal to promote repair of myelin.
Living a healthy lifestyle can potentially allow people living with MS to take charge of their disease. To provide guidance to individuals with MS, the Society reached out to experts and those living with MS to create the MS Wellness Toolkit. The toolkit can be accessed on our website.The Society also has information on research that is examining if and how physical activity affects the MS disease course, emotional health, and overall well-being
Source:
Jensen S et al. (2018) Multimodal Enhancement of Remyelination by Exercise with a Pivotal Role for Oligodendroglial PGC1α. Cell Rep. 24(12):3167-3179.