Voluntary Running Triggers VGF-Mediated Oligodendrogenesis to Prolong the Lifespan of Snf2h-Null Ataxic Mice
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Fecha
2016-10
Profesor/a Guía
Facultad/escuela
Idioma
en
Título de la revista
ISSN de la revista
Título del volumen
Editor
CELL PRESS
Nombre de Curso
Licencia CC
Licencia CC
Resumen
Exercise has been argued to enhance cognitive function and slow progressive neurodegenerative disease. Although exercise promotes neurogenesis, oligodendrogenesis and adaptive myelination are also significant contributors to brain repair and brain health. Nonetheless, the molecular details underlying these effects remain poorly understood. Conditional ablation of the Snf2h gene impairs cerebellar development producing mice with poor motor function, progressive ataxia, and death between postnatal days 25-45. Here, we show that voluntary running induced an endogenous brain repair mechanism that resulted in a striking increase in hindbrain myelination and the long-term survival of Snf2h cKO mice. Further experiments identified the VGF growth factor as a major driver underlying this effect. VGF neuropeptides promote oligodendrogenesis in vitro, whereas Snf2h cKO mice treated with full-length VGF-encoding adenoviruses removed the requirement of exercise for survival. Together, these results suggest that VGF delivery could represent a therapeutic strategy for cerebellar ataxia and other pathologies of the CNS.
Notas
Indexación: Web of Science
Palabras clave
HIPPOCAMPAL NEUROGENESIS, ADENOVIRUS VECTORS, NEUROPEPTIDE VGF, PROGENITOR CELLS, PRECURSOR CELLS, SPATIAL MEMORY, DENTATE GYRUS, EARLY PHASE, GENE VGF, EXERCISE
Citación
CELL REPORTS, 17 (3):862-875