期刊
STEM CELL REPORTS
卷 12, 期 6, 页码 1313-1328出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2019.04.010
关键词
-
资金
- JSPS KAKENHI [JP18K06469, JP26117007]
Neurogenesis in specific brain regions in adult mammals decreases with age. Progressive reduction in the proliferation of neural stem and progenitor cells (NS/PCs) is a primary cause of this age-associated decline. However, the mechanism responsible for this reduction is poorly understood. We identify p38 MAPK as a key factor in the proliferation of neural progenitor cells (NPCs) in adult neurogenic niches. p38 expression in adult NS/PCs is downregulated during aging. Deletion of p38 alpha in NS/PCs specifically reduces the proliferation of NPCs but not stem cells. Conversely, forced expression of p38 alpha, in NS/PCs in the aged mouse subventricular zone (SVZ) restores NPC proliferation and neurogenesis, and prevents age-dependent SVZ atrophy. We also found that p38 is necessary for suppressing the expression of Wnt antagonists DKK1 and SFRP3, which inhibit the proliferation of NPCs. Age-related reduction in p38 thus leads to decreased adult neurogenesis via downregulation of Wnt signaling.
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