2019年6月11日
Involvement of p38 in Age-Related Decline in Adult Neurogenesis via Modulation of Wnt Signaling
Stem Cell Reports
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- ,
- ,
- 巻
- 12
- 号
- 6
- 開始ページ
- 1313
- 終了ページ
- 1328
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.stemcr.2019.04.010
- 出版者・発行元
- Stem Cell Reports
© 2019 The Author(s) 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 p38α in NS/PCs specifically reduces the proliferation of NPCs but not stem cells. Conversely, forced expression of p38α 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. Kase et al. show that p38 expression in neural stem and progenitor cells (NS/PCs) in the adult brain decreases with aging. This reduction specifically causes proliferation defect i
- リンク情報
- ID情報
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- DOI : 10.1016/j.stemcr.2019.04.010
- ISSN : 2213-6711
- PubMed ID : 31080114
- PubMed Central 記事ID : PMC6565990