Sex and age differences in glia and myelin in nonhuman primate and human spinal cords: implications for pathology

Abstract In a healthy central nervous system, glial cells are influenced by genetic, epigenetic, age, and sex factors. Aging typically causes astrocytes and microglia to undergo changes that reduce their neuroprotective functions and increase harmful activities. Additionally, sex-related differences in glial and myelin functions may impact neurological disorders. Despite this, few studies have investigated glial cells in primates, with most focusing on the brain. This study aims to explore whether glial cells and myelin exhibit age- and sex-related differences in the spinal cord of nonhuman primates and humans. We used immunohistochemistry and myelin staining to analyze healthy spinal cord samples from midlife and aged individuals of both sexes, focusing on Microcebus murinus (a small nonhuman primate) and humans. Primate spinal cords show distinct variations in glial markers and myelin characteristics related to sex and age, with differences varying between species. Notably, GFAP expression is sex-dependent in both primate species. We also observed greater differences in the expression of microglial markers than other glial markers. Overall, we found the opposite pattern for the g-ratio and oligodendrocytic marker between species. These findings suggest that glial cells may play a critical role in age- and sex-related differences in the prevalence and progression of spinal cord diseases.