2. Academic Validation
  3. Aged lipid-laden microglia display impaired responses to stroke

Aged lipid-laden microglia display impaired responses to stroke

  • EMBO Mol Med. 2022 Dec 21;e17175. doi: 10.15252/emmm.202217175.
Maria Arbaizar-Rovirosa 1 2,  Jordi Pedragosa 1 2,  Juan J Lozano 3,  Carme Casal 4,  Albert Pol 2 5 6,  Mattia Gallizioli 1 2,  Anna M Planas 1 2
Affiliations

Affiliations

  • 1 Department of Neuroscience and Experimental Therapeutics, Instituto de Investigaciones Biomédicas de Barcelona (IIBB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain.
  • 2 Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • 3 Bioinformatics Platform, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
  • 4 Microscopy Service, Instituto de Investigaciones Biomédicas de Barcelona (IIBB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain.
  • 5 Department of Biomedical Sciences, Faculty of Medicine, Universitat de Barcelona, Barcelona, Spain.
  • 6 Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
PMID: 36541061 DOI: 10.15252/emmm.202217175
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.

Keywords

brain; immunometabolism; ischemia; lipid droplets; microglia.

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