As the brain's soldiers grow older: aging microglia within the pineal gland

Abstract

Microglia are resident immune cells of the central nervous system (CNS). They not only defend the CNS from insults, but they also contribute to the brain ontogeny and homeostasis. In the developing pineal gland (PG), microglia are a dynamic population that make active contact with pineal precursor cells and other constituent elements. These interactions modulate the fate, density and activity of pineal elements as they develop. For the aging CNS, microglia shift into an altered phenotype. In this study, we tried to characterize the aging microglia in PG from 18-month-old rats. Our analysis against 3-month-old rats showed a slight but significant decrease in the density of microglia-like Iba1þ cells in the old PG. Their proliferative capacity was also significantly reduced based on the levels of the nuclear marker PCNA. However, heterogeneity in PCNA expression among Iba1þ cells was observed at both ages. In the aged Iba1þ cells, we noted a spectrum in the expression pattern of the lysosomal marker ED1 from discreet cytoplasmic ED1þ bodies to enormous and deforming ED1þ structures. Also, we found that the density of the precursor-like Pax6þ cells decreased during aging, but the percentage of contacts between Iba1þ and Pax6þ cells remained stable from adulthood to old age. Our results illustrate some of the changes experienced by the pineal microglia during aging. These impacts within the pineal microenvironment could affect the overall physiology of the gland as it ages.