Multimodal Enhancement of Remyelination by Exercise with a Pivotal Role for Oligodendroglial PGC1α.
Cell Rep
; 24(12): 3167-3179, 2018 09 18.
Article
en En
| MEDLINE
| ID: mdl-30232000
ABSTRACT
Remyelination is a multistep regenerative process that results in the reformation of myelin sheaths around demyelinated axons and is a critical therapeutic target. Here we show that immediate access to a running wheel following toxin-induced demyelination in mice enhances oligodendrogenesis, the rate of remyelination, and the proportion of remyelinated axons. RNA sequencing suggests broad activation of pro-remyelination pathways including phagocytosis by exercise and highlights peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC1α) activation. By immunohistochemistry and cell type-specific conditional deletion, we confirmed PGC1α within oligodendrocytes as a transiently expressed factor required for the rate of myelin thickening by exercise. We validated the exercise-enhanced clearance of inhibitory lipid debris from lesions. Finally, exercise works in parallel with the remyelinating medication clemastine to produce complete remyelination of lesions. Our study demonstrates physical activity as an integrative means to enhance remyelination and details a multimodal mechanism including the pivotal PGC1α-dependent enhancement of myelin thickness.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Condicionamiento Físico Animal
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Oligodendroglía
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Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma
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Remielinización
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Vaina de Mielina
Límite:
Animals
Idioma:
En
Revista:
Cell Rep
Año:
2018
Tipo del documento:
Article
País de afiliación:
Canadá