دورية أكاديمية
Ultrastructural characterization of dark microglia during aging in a mouse model of Alzheimer's disease pathology and in human post-mortem brain samples
| العنوان: | 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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| المؤلفون: | St-Pierre, Marie-Kim, Carrier, Micaël, González Ibáñez, Fernando, Šimončičová, Eva, Wallman, Marie-Josée, Vallières, Luc, Parent, Martin, Tremblay, Marie-Ève |
| بيانات النشر: | Journal of Neuroinflammation |
| سنة النشر: | 2022 |
| المجموعة: | University of Victoria (Canada): UVicDSpace |
| مصطلحات موضوعية: | Microglia, Dark microglia, Ultrastructure, Alzheimer's disease, Human post-mortem brain samples, Dystrophic neurites, Amyloid-beta |
| الوصف: | 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. ; MKSP 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. ; Faculty ; Reviewed |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | 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/s12974-022-02595-8Test; https://doi.org/10.1186/s12974-022-02595-8Test; http://hdl.handle.net/1828/14671Test |
| DOI: | 10.1186/s12974-022-02595-8 |
| الإتاحة: | https://doi.org/10.1186/s12974-022-02595-8Test http://hdl.handle.net/1828/14671Test |
| رقم الانضمام: | edsbas.151FF8BC |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12974-022-02595-8 |
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