Early loss of astrocyte p38α MAPK reduces hippocampal neuroinflammation, enhances synaptic strength, and increases non-synaptic mitochondrial uncoupling in female mice during non-pathological aging

We found that early loss of astrocyte p38α was associated with a reduction in hippocampal neuroinflammation and concomitant enhancement of synaptic strength in aged female mice. In subsequent experiments in younger animals, the knockout reduced peripheral GFAP levels and increased non-synaptic mitochondrial uncoupling. These findings indicate that astrocyte p38α has wide-ranging effects on brain metabolism, inflammation, and synaptic function during the course of normal aging, including release of GFAP from the central nervous system to the periphery.

Follow-up studies exploring the role of astrocyte p38α in various age-associated neuropathological contexts are warranted.