Year: 2022
Type: article
Abstract: 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.
Source: EMBO Molecular Medicine
Institutions: Consejo Superior de Investigaciones Científicas, Institut d'Investigacions Biomèdiques de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institució Catalana de Recerca i Estudis Avançats, Universitat de Barcelona
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,300
Funders: Centres de Recerca de Catalunya, European Commission, Generalitat de Catalunya, Ministerio de Ciencia e Innovación, Universitat de Barcelona, Plexxikon, Consejo Superior de Investigaciones Científicas, European Regional Development Fund, Agencia Estatal de Investigación, European Social Fund
Awards: G1175115578, G1352864293, G1622782223, G1716570160, G210041235, G2262748287, G2522753747, G2601397997, G2753695834, G300979063, G3022609761, G34346518, G3480869486, G3681454997, G4042783231, G410571670, G425668148, G4442677895, G451917667, G4526231891, G5080475149, G5805502524, G5967599077, G6080697404, G6218905885, G7084143925, G929308097
OpenAlex ID: W4312066749