Elevated p38MAPK activity promotes neural stem cell aging

Aging (Albany NY). 2020 Apr 3;12(7):6030-6036. doi: 10.18632/aging.102994. Epub 2020 Apr 3.

Abstract

Age-progressive neural stem cell (NSC) dysfunction leads to impaired neurogenesis, cognitive decline and the onset of age-related neurodegenerative pathologies. p38MAPK signalling pathway limits stem cell activity during aging in several tissues. Its role in NSCs remains controversial. In this work, we show that p38MAPK activity increases in NSCs with age in the subventricular zone (SVZ) and its pharmacological inhibition is sufficient to rejuvenate their activity in vitro. These data reveal a cell-autonomous role for p38MAPK increase in decreasing NSC homeostasis with age. This information shed light in the role of p38MAPK in NSC aging.

Keywords: aging; neural stem cell; p38MAPK; pharmacological inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging* / drug effects
  • Aging* / metabolism
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Benzamides / pharmacology*
  • Lateral Ventricles / metabolism
  • MAP Kinase Signaling System / drug effects*
  • Mice
  • Neural Stem Cells / metabolism*
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / metabolism
  • Neurogenesis / drug effects
  • Neurogenesis / physiology
  • Pyridones / pharmacology*
  • p38 Mitogen-Activated Protein Kinases* / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases* / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzamides
  • PH 797804
  • Pyridones
  • p38 Mitogen-Activated Protein Kinases