Open AccessNeuronal p38α mediates age‐associated neural stem cell exhaustion and cognitive decline
Author(s) -
MorenoCug Leire,
Revuelta Miren,
Arrizabalaga Olatz,
Colie Sandra,
MorenoValladares Manuel,
JimenezBlasco Daniel,
GilBea Francisco,
Llarena Irantzu,
Bolaños Juan Pedro,
Nebreda Angel R.,
Matheu Ander
Publication year - 2019
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13044
Subject(s) - biology , neural stem cell , subventricular zone , neuroscience , hippocampus , cognitive decline , cognition , p38 mitogen activated protein kinases , limiting , premovement neuronal activity , stem cell , neurogenesis , microbiology and biotechnology , signal transduction , medicine , dementia , mapk/erk pathway , mechanical engineering , disease , engineering
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.