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- Title
Ultrastructural characterization of dark microglia during aging in a mouse model of Alzheimer's disease pathology and in human post-mortem brain samples.
- Authors
St-Pierre, Marie-Kim; Carrier, Micaël; González Ibáñez, Fernando; Šimončičová, Eva; Wallman, Marie-Josée; Vallières, Luc; Parent, Martin; Tremblay, Marie-Ève; González Ibáñez, Fernando
- Abstract
A 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.
- Publication
Journal of Neuroinflammation, 2022, Vol 19, Issue 1, p1
- ISSN
1742-2094
- Publication type
Article
- DOI
10.1186/s12974-022-02595-8