Poststroke lipid droplet accumulation in residing microglia and its influence on inflammation
von Wei Wei
Datum der mündl. Prüfung:2023-10-19
Betreuer:Prof. Dr. Thorsten Roland Döppner
Gutachter:Prof. Dr. Thorsten Roland Döppner
Gutachter:Prof. Dr. Michael Werner Sereda
EnglischMicroglia are critically involved in poststroke inflammation and thus affect neurological outcomes. Lipid droplet (LD) accumulation of microglia is dysfunctional in the aged brain and contributes to the worse outcome of neurodegenerative disorders. However, the role of such LD-rich microglia (LDRM) under stroke conditions is unknown. Using both, in vitro and in vivo stroke models, we herein studied accumulation patterns of microglial LD and their corresponding microglial inflammatory signaling cascades. We also studied mutual interactions between lipid profile dynamics and microglial phenotypes in different poststroke brain regions. As such, microglia display enhanced levels of LD accumulation and elevated perilipin 2 (PLIN2) expression patterns when exposed to hypoxia or stroke. Such LDRM exhibit high levels of the cytokines TNF-α, IL-6, and IL-1β as well as a pro-inflammatory phenotype and differentially expressed lipid metabolism-related genes. In line with this, post-ischemic alterations of lipid metabolism result in distinct lipid profiles with spatial and temporal dynamics, especially with regard to cholesteryl ester and triacylglycerol levels. This distinct lipid pattern further exacerbates post-ischemic inflammation. The present study sheds new light into the dynamic changes of brain lipid profiles and aggregation patterns of LD in microglia exposed to stroke, demonstrating a mutual mechanism between microglial phenotype and function, which contributes to secondary progression of brain injury upon stroke.
Keywords: cholesteryl ester; inflammation; lipid droplet; ischemic stroke; microglia; lipidomics