Increased white matter microglial reaction and perivascular macrophages in the aging microcebe primate

Abstract

Microglia are the resident macrophages of the central nervous system. They play crucial roles in maintaining brain homeostasis, yet their involvement in aging remains not fully understood. While age-related microglia changes have been strongly characterized in rodents, studies in non-human primates are scarce. HLA-DR is a major histocompatibility class II cell surface receptor which presents antigens to cell of the immune response. It is a major marker of microglia reaction. In this study, we explored microglia in the brain of a non-human primate (mouse lemur (Microcebus murinus)) using HLA-DR immunolabeling. We analyzed microglial morphology and quantified HLA-DR+ cell density and protein expression in middle-aged and old animals. A wide range of microglial morphologies was observed in the white matter, including thin processes microglia, rod-like elongated and polarized shape, hypertrophic, and amoeboid microglia. Aging was associated with a region-specific regulation of microglia as increased HLA-DR+ microglial expression was found in the white matter while very few HLA-DR+ microglia were observed in the parenchyma of cortical gray matter regions. A second finding of the study was the higher number of HLA-DR+ perivascular macrophages in old animals. Although further studies are required to investigate the cause of these age-related changes, this study is critical as it describes for the first time the microglial and perivascular macrophage status in microcebus murinus primate that is widely used as a model for cerebral aging and to investigate age-related neurodegenerative processes.