Ultrastructural characterization of dark microglia during aging in a mouse model of Alzheimer's disease pathology and in human post-mortem brain samples
Date
2022
Authors
St-Pierre, Marie-Kim
Carrier, Micaël
González Ibáñez, Fernando
Šimončičová, Eva
Wallman, Marie-Josée
Vallières, Luc
Parent, Martin
Tremblay, Marie-Ève
Journal Title
Journal ISSN
Volume Title
Publisher
Journal of Neuroinflammation
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.
Description
Keywords
Microglia, Dark microglia, Ultrastructure, Alzheimer's disease, Human post-mortem brain samples, Dystrophic neurites, Amyloid-beta, Centre for Advanced Materials and Related Technology (CAMTEC)
Citation
St-Pierre, M., Carrier, M., González Ibáñez, F., Šimončičová, E., Wallman, M., Vallières, L, . . . Tremblay, M. (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/s12974-022-02595-8