Aged lipid-laden microglia display impaired responses to stroke.
Maria Arbaizar-RovirosaJordi PedragosaJuan José LozanoCarme CasalAlbert PolMattia GallizioliAnna M PlanasPublished in: EMBO molecular medicine (2022)
Microglial cells of the aged brain manifest signs of dysfunction that could contribute to the worse neurological outcome of stroke in the elderly. Treatment with colony-stimulating factor 1 receptor antagonists enables transient microglia depletion that is followed by microglia repopulation after treatment interruption, causing no known harm to mice. We tested whether this strategy restored microglia function and ameliorated stroke outcome in old mice. Cerebral ischemia/reperfusion induced innate immune responses in microglia highlighted by type I interferon and metabolic changes involving lipid droplet biogenesis. Old microglia accumulated lipids under steady state and displayed exacerbated innate immune responses to stroke. Microglia repopulation in old mice reduced lipid-laden microglia, and the cells exhibited reduced inflammatory responses to ischemia. Moreover, old mice with renewed microglia showed improved motor function 2 weeks after stroke. We conclude that lipid deposits in aged microglia impair the cellular responses to ischemia and worsen functional recovery in old mice.
Keyphrases
- inflammatory response
- neuropathic pain
- immune response
- atrial fibrillation
- high fat diet induced
- cerebral ischemia
- induced apoptosis
- toll like receptor
- fatty acid
- lipopolysaccharide induced
- spinal cord injury
- dendritic cells
- subarachnoid hemorrhage
- spinal cord
- type diabetes
- adipose tissue
- cell cycle arrest
- oxidative stress
- signaling pathway
- insulin resistance
- drug induced
- brain injury
- skeletal muscle
- preterm birth
- cerebral blood flow