| First Author | Kase Y | Year | 2019 |
| Journal | Stem Cell Reports | Volume | 12 |
| Issue | 6 | Pages | 1313-1328 |
| PubMed ID | 31080114 | Mgi Jnum | J:295565 |
| Mgi Id | MGI:6453971 | Doi | 10.1016/j.stemcr.2019.04.010 |
| Citation | Kase Y, et al. (2019) Involvement of p38 in Age-Related Decline in Adult Neurogenesis via Modulation of Wnt Signaling. Stem Cell Reports 12(6):1313-1328 |
| abstractText | 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 p38alpha in NS/PCs specifically reduces the proliferation of NPCs but not stem cells. Conversely, forced expression of p38alpha 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. |
