King's College London

Research portal

Involvement of p38 in Age-Related Decline in Adult Neurogenesis via Modulation of Wnt Signaling

Research output: Contribution to journalArticle

Yoshitaka Kase, Kinya Otsu, Takuya Shimazaki, Hideyuki Okano

Original languageEnglish
Pages (from-to)1313–1328
Number of pages16
JournalStem Cell Reports
Volume12
Issue number6
Early online date9 May 2019
DOIs
Publication statusPublished - 11 Jun 2019

Documents

King's Authors

Abstract

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 in neural progenitor cells (NPCs), leading to the age-dependent decline of adult neurogenesis. Conversely, overexpression of p38α in NS/PCs in the aged brain restores NPC proliferation without exhaustion of neural stem cells.

Download statistics

No data available

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454