Aging and sex: Impact on microglia phagocytosis

Abstract

Microglia are the primary innate immune cells of the brain and are key players in the resolution or propagation of the inflammatory process (Kettenmann, Hanisch, Noda, & Verkhratsky, 2011; Ransohoff & Perry, 2009). These glial cells perform central functions in the regulation of cell number, synaptic patterning, homeostasis maintenance, and response to pathogens by selective phagocytosis. Microglia phagocytosis is a fine-tuned process mediated by the expression of specific receptors on the cell surface and downstream signaling pathways that, depending on their ability to recognize misfolded proteins and apoptotic cells or bind structurally conserved molecules derived from microbial pathogens (such as Toll-like receptors; TLRs), contribute to the engulfment of cellular debris, harmful particles, or synapses (Fu,

Interplay Between Microglia and Alzheimer’s Disease—Focus on the Most Relevant Risks: APOE Genotype, Sex and Age

“…Microglial process speed significantly decreases with age (Streit et al, 2004;Olah et al, 2018). The changes in the phagocytic activity of senescent microglia in vitro were similar to those of microglia purified from aged brains (Yanguas-Casas et al, 2020). In vivo imaging of young, adult, and aging mice showed that in addition to a slight increase in cell density, microglial morphology and behavior also changed (e.g., larger cell bodies, shorter dendrites, thicker dendrites, fewer branches, and decreased phagocytic ability and motor ability; Figure 2; McGeer et al, 1987;Itagaki et al, 1989;Styren et al, 1990).…”

“…In contrast, the microglia of male newborn animals exhibited higher internalization of E. coli bioparticles than the microglia of female newborn animals (Figure 1; Yanguas-Casas et al, 2020). However, these sex differences disappeared in microglia isolated from the brains of adults (5 months;Yanguas-Casas et al, 2020). Given the above findings, we believe that the sex differences in microglia are mainly reflected during the developmental stage.…”

“…Microglial coverage of plaques was highest in male APOE3 mice, while the microglial coverage observed in APOE4 mice and female mice was significantly lower, meanwhile the amyloid level was increased (Stephen et al, 2019). It has been reported that the aged microglia of female mice may lost the ability to adapt their phagocytosis to inflammatory conditions (Yanguas-Casas et al, 2020). With aging, estrogen resistance may be related to the impaired ability of microglia to reduce inflammation.…”

“…Microglia isolated from the brains of newborn female animals exhibited a higher degree of basic internalization of fluorescent beads and nerve debris than male microglia (Figure 1; Yanguas-Casas et al, 2020). In contrast, the microglia of male newborn animals exhibited higher internalization of E. coli bioparticles than the microglia of female newborn animals (Figure 1; Yanguas-Casas et al, 2020). However, these sex differences disappeared in microglia isolated from the brains of adults (5 months;Yanguas-Casas et al, 2020).…”

“…In addition, females have a higher rate of phagocytosis of neural precursor cells and healthy cells than males (Figure 1; Nelson et al, 2017). Microglia isolated from the brains of newborn female animals exhibited a higher degree of basic internalization of fluorescent beads and nerve debris than male microglia (Figure 1; Yanguas-Casas et al, 2020). In contrast, the microglia of male newborn animals exhibited higher internalization of E. coli bioparticles than the microglia of female newborn animals (Figure 1; Yanguas-Casas et al, 2020).…”