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
Mice RBRC02192 RBRC05147