Brain Injury Accelerates the Onset of a Reversible Age-Related Microglial Phenotype Associated With Inflammatory Neurodegeneration

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

Publication Date

3-10-2023

Journal

Science Advances

Abstract

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

Keywords

Animals, Mice, Microglia, Mice, Inbred C57BL, Brain Injuries, Brain Injuries, Traumatic, Brain, Phenotype, Lipids