Reference - Detail
| RRC ID | 57665 |
|---|---|
| Author | Kase Y, Otsu K, Shimazaki T, Okano H. |
| Title | Involvement of p38 in Age-Related Decline in Adult Neurogenesis via Modulation of Wnt Signaling. |
| Journal | Stem Cell Reports |
| 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. |
| Volume | 12(6) |
| Pages | 1313-1328 |
| Published | 2019-6-11 |
| DOI | 10.1016/j.stemcr.2019.04.010 |
| PII | S2213-6711(19)30132-8 |
| PMID | 31080114 |
| PMC | PMC6565990 |
| MeSH | Aging / metabolism* Aging / pathology Animals Homeodomain Proteins / metabolism Humans Mice Mice, Transgenic Motor Neurons / metabolism Motor Neurons / pathology Mouse Embryonic Stem Cells / metabolism* Mouse Embryonic Stem Cells / pathology Neural Stem Cells / metabolism* Neural Stem Cells / pathology Neurogenesis* Proto-Oncogene Proteins c-akt / metabolism Wnt Signaling Pathway* p38 Mitogen-Activated Protein Kinases / genetics p38 Mitogen-Activated Protein Kinases / metabolism* |
| IF | 6.032 |
| Times Cited | 10 |
| Resource | |
| Mice | RBRC02192 RBRC05147 |