Microglial phagocytosis dysfunction in stroke is driven by energy depletion and induction of autophagy.

ABSTRACT: Microglial phagocytosis of apoptotic debris prevents buildup damage of neighbor neurons and inflammatory responses. Whereas microglia are very competent phagocytes under physiological conditions, we report their dysfunction in mouse and preclinical monkey models of stroke (macaques and marmosets) by transient occlusion of the medial cerebral artery (tMCAo). By analyzing recently published bulk and single cell RNA sequencing databases, we show that the phagocytosis dysfunction was not explained by transcriptional changes. In contrast, we demonstrate that the impairment of both engulfment and degradation was related to energy depletion triggered by oxygen and nutrient deprivation (OND), which led to reduced process motility, lysosomal exhaustion, and the induction of a protective macroautoph

SUBMITTER: Beccari S 

PROVIDER: S-EPMC10283420 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature