Neuronal activity regulates cognition and neural stem cell (NSC) function. The molecular pathways limiting neuronal activity during aging remain largely unknown. In this work, we show that p38MAPK activity increases in neurons with age. By using mice expressing p38α-lox and CamkII-Cre alleles (p38α∆-N), we demonstrate that genetic deletion of p38α in neurons suffices to reduce age-associated elevation of p38MAPK activity, neuronal loss and cognitive decline. Moreover, aged p38α∆-N mice present elevated numbers of NSCs in the hippocampus and the subventricular zone. These results reveal novel roles for neuronal p38MAPK in age-associated NSC exhaustion and cognitive decline.
Keywords: aging; cognitive decline; neural stem cells; neuronal activity; p38MAPK.
© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.