Brain injury accelerates the onset of a reversible age-related microglial phenotype associated with inflammatory neurodegeneration

• DOI: 10.1126/sciadv.add1101
• Publication Date: 2023-03-08T18:57:16Z
• Authors: Rodney M. Ritzel; Yun Li; Yun Jiao; Zhuofan Lei; Sarah J. Doran; Junyun He; Rami A. Shahror; Rebecca J. Henry; Romeesa Khan; Chunfeng Tan; Shaolin Liu; Bogdan A. Stoica; Alan I. Faden; Gregory Szeto; David J. Loane; Junfang Wu
• Keywords: Lipofuscin

Lipofuscin is an autofluorescent (AF) pigment formed by lipids and misfolded proteins, which accumulates in postmitotic cells with advanced age. Here, we immunophenotyped microglia the brain of old C57BL/6 mice (>18 months old) demonstrate that comparison to young mice, one-third are AF, characterized profound changes lipid iron content, phagocytic activity, oxidative stress. Pharmacological depletion eliminated AF following repopulation reversed microglial dysfunction. Age-related neurological deficits neurodegeneration after traumatic injury (TBI) were attenuated lacking microglia. Furthermore, increased lysosomal burden, accumulation persisted for up 1 year TBI, modified APOE4 genotype, chronically driven phagocyte-mediated Thus, may reflect a pathological state aging associated phagocytosis neurons myelin inflammatory can be further accelerated TBI.