As the Brain's Soldiers Grow Older: Aging Microglia within the Pineal Gland

E. M. MUÑOZ; C. L. FREITES

Carlos Paz, Córdoba

Congreso; XXXIV Congress of the Argentine Society for Research in Neuroscience; 2019

Sociedad Argentina de Investigación en Neurociencias (SAN)

Microglia are resident immune cells of the central nervous system (CNS), where they play multiple roles. Microglia not only defend the CNS from insults, but they also contribute to the brain ontogeny and homeostasis. For instance, in the developing pineal gland (PG), a circumventricular organ, microglia are a plastic and dynamic population that make active contact with pineal precursor cells and other constituent elements, such as nerve fibers and blood vessels. These interactions modulate the fate, density and activity of these pineal elements as they develop. In this way, microglia are true "cellular engineers" for their crucial role in tissue modeling. For the aging CNS, microglia shift into an altered phenotype. In this study, we used multiple immunofluorescence staining followed by quantitative confocal microscopy to characterize the aging microglia in PG from 18-month-old Wistar rats. Our morphometric analysis against 3-month-old rats showed a slight but significant decrease in the density of microglia-like Iba1+ 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 Iba1+ cells was observed at both ages, suggesting that they retained certain replicative capacity during aging. In the aged Iba1+ cells, we also noted a spectrum in the expression pattern of the lysosomal marker ED1/CD68 from discreet and small cytoplasmic ED1+ bodies to enormous and deforming ED1+ structures that occasionally protruded from the cellular surface. Furthermore, we found that the density of the precursor-like Pax6+ cells decreased during aging, but the percentage of contacts between Iba1+ and Pax6+ cells, and phagocytic events 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, including the synthesis of the melatonin hormone.