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Voluntary physical activity enhances remyelination in mice after spinal cord demyelination: mechanisms of benefit of exercise for repair
S. Jensen, V.W. Yong University of Calgary, Calgary, AB, Canada
Objective: To determine whether physical activity leads to the promotion of remyelination in mice after experimental demyelination, and to investigate mechanisms underpinning the benefits of physical activity.
Background: A large body of literature has now established that physical activity promotes wellbeing in multiple sclerosis (MS). However, whether physical activity induces reparative processes including remyelination of a demyelinated plaque is unknown. We evaluated whether mice with spinal cord demyelination have improved remyelinating capacity if these animals were allowed voluntary physical activity after injury. If so, we sought to uncover biological mechanisms underlying exercise-induced repair.
Methods: We induced a focal demyelinating lesion by injection of lysolecithin into the ventrolateral white matter of the murine spinal cord. Mice were singly housed and given free access to an electronically monitored running wheel, which were locked in control animals, immediately after injury until sacrifice at either 3, 7 or 14 days post lesion (dpl). Spinal cord tissues were processed for various analyses.
Results: Immediate access to a running wheel enhances oligodendrocyte generation following a lysolecithin-induced demyelinating insult; we observed a 39% and 30% increase in oligodendrocytes at 7 and 14 dpl, respectively. At 7 dpl, the % of PDGFRα+ progenitors that label for the proliferation marker Ki67 was elevated in the exercise compared to sedentary demyelinated animals (p< 0.01). At 14 dpl, these newly formed progenitors functionally differentiate into CC1+ mature oligodendrocytes in active mice. Moreover, exercise increases the capacity for individual oligodendrocytes to form myelin segments resulting in a 2.7 fold elevation in the number of myelinated axons at 14 dpl. Several mechanisms appear to contribute to exercise-enhanced remyelination, including an altered local inflammation, and elevated expression within oligodendrocyte lineage cells of PPARgamma co-activator 1-alpha (PGC1a), a transcriptional co-activator that regulates genes involved in lipid and energy metabolism.
Conclusions: Physical exercise improves white matter regeneration and may help account for activity-enhanced wellbeing in patients with MS.
S. Jensen, V.W. Yong University of Calgary, Calgary, AB, Canada
Objective: To determine whether physical activity leads to the promotion of remyelination in mice after experimental demyelination, and to investigate mechanisms underpinning the benefits of physical activity.
Background: A large body of literature has now established that physical activity promotes wellbeing in multiple sclerosis (MS). However, whether physical activity induces reparative processes including remyelination of a demyelinated plaque is unknown. We evaluated whether mice with spinal cord demyelination have improved remyelinating capacity if these animals were allowed voluntary physical activity after injury. If so, we sought to uncover biological mechanisms underlying exercise-induced repair.
Methods: We induced a focal demyelinating lesion by injection of lysolecithin into the ventrolateral white matter of the murine spinal cord. Mice were singly housed and given free access to an electronically monitored running wheel, which were locked in control animals, immediately after injury until sacrifice at either 3, 7 or 14 days post lesion (dpl). Spinal cord tissues were processed for various analyses.
Results: Immediate access to a running wheel enhances oligodendrocyte generation following a lysolecithin-induced demyelinating insult; we observed a 39% and 30% increase in oligodendrocytes at 7 and 14 dpl, respectively. At 7 dpl, the % of PDGFRα+ progenitors that label for the proliferation marker Ki67 was elevated in the exercise compared to sedentary demyelinated animals (p< 0.01). At 14 dpl, these newly formed progenitors functionally differentiate into CC1+ mature oligodendrocytes in active mice. Moreover, exercise increases the capacity for individual oligodendrocytes to form myelin segments resulting in a 2.7 fold elevation in the number of myelinated axons at 14 dpl. Several mechanisms appear to contribute to exercise-enhanced remyelination, including an altered local inflammation, and elevated expression within oligodendrocyte lineage cells of PPARgamma co-activator 1-alpha (PGC1a), a transcriptional co-activator that regulates genes involved in lipid and energy metabolism.
Conclusions: Physical exercise improves white matter regeneration and may help account for activity-enhanced wellbeing in patients with MS.