Ultrastructural characterization of dark microglia during aging in a mouse model of Alzheimer's disease pathology and in human post-mortem brain samples

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dc.contributor.authorSt-Pierre, Marie-Kim
dc.contributor.authorCarrier, Micaël
dc.contributor.authorGonzález Ibáñez, Fernando
dc.contributor.authorŠimončičová, Eva
dc.contributor.authorWallman, Marie‑Josée
dc.contributor.authorVallières, Luc
dc.contributor.authorParent, Martin
dc.contributor.authorTremblay, Marie-Ève
dc.date.accessioned2024-02-12T23:33:54Z
dc.date.available2024-02-12T23:33:54Z
dc.date.copyright2022en_US
dc.date.issued2022
dc.descriptionWe would like to thank Dr. Nathalie Vernoux and Hassan El Hajj for their help with the perfusion of the mice.en_US
dc.description.abstractA diverse heterogeneity of microglial cells was previously described in Alzheimer’s disease (AD) pathology, including dark microglia, a state characterized by ultrastructural markers of cellular stress. To provide novel insights into the roles of dark microglia during aging in the context of AD pathology, we performed a quantitative density and ultrastructural analysis of these cells using high-throughput scanning electron microscopy in the ventral hippocampus CA1 stratum lacunosum-moleculare of 20-month-old APP-PS1 vs C57BL/6J male mice. The density of dark microglia was significantly higher in APP-PS1 vs C57BL/6J mice, with these cells accounting for nearly half of all microglia observed near amyloid-beta (Aβ) plaques. This dark microglial state interacted more with dystrophic neurites compared to other APP-PS1 microglia and possessed glycogen granules, associated with a metabolic shift toward glycolysis, which provides the first ultrastructural evidence of their presence in microglia. Dark microglia were further observed in aging human post-mortem brain samples showing similar ultrastructural features as in mouse. Overall, our results provide a quantitative ultrastructural characterization of a microglial state associated with cellular stress (i.e., dark microglia) that is primarily restricted near Aβ plaques and dystrophic neurites. The presence of this microglial state in the aging human post-mortem brain is further revealed.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipMKSP is supported by doctoral training awards from the Canadian Institutes of Health Research (CIHR) and Fonds de recherche du Québec – Santé (FRQS). MC holds a FRQS doctoral’s training award. ES is a recipient of the Branch Out Foundation Graduate Grant and a Faculty of Graduate Studies (University of Victoria) Graduate Scholarships. MET holds a Canada Research Chair (Tier 2) in Neurobiology of Aging and Cognition. This work was funded by a CIHR Foundation grant (FDN341846) awarded to MET.en_US
dc.identifier.citationSt-Pierre, M-K., Carrier, M., González Ibáñez, F., Wallman, M-J., Vallières, L., Parent, M., & Tremblay, M-È. (2022). Ultrastructural characterization of dark microglia during aging in a mouse model of Alzheimer's disease pathology and in human post-mortem brain samples. Journal of Neuroinflammation, 19(235). https://doi.org/10.1186/s12974-022-02595-8en_US
dc.identifier.urihttps://doi.org/10.1186/s12974-022-02595-8
dc.identifier.urihttp://hdl.handle.net/1828/15992
dc.language.isoenen_US
dc.publisherJournal of Neuroinflammationen_US
dc.subjectAlzheimer's disease
dc.subjectmicroglia
dc.subjectdark microglia
dc.subjectultrastructure
dc.subjecthuman post-mortem brain samples
dc.subjectdystrophic neurites
dc.subjectamyloid-beta
dc.subjectCentre for Advanced Materials and Related Technology (CAMTEC)
dc.subject.departmentDivision of Medical Sciences
dc.subject.departmentSchool of Medical Sciences
dc.titleUltrastructural characterization of dark microglia during aging in a mouse model of Alzheimer's disease pathology and in human post-mortem brain samplesen_US
dc.typeArticleen_US

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