Brain, Behavior, & Immunity - Health (Jan 2020)
Astrocytic response to neural injury is larger during development than in adulthood and is not predicated upon the presence of microglia
Abstract
While contributions of microglia and astrocytes are regularly studied in various injury models, how these contributions differ across development remains less clear. We previously demonstrated developmental differences in microglial profiles across development in an injury model of the gustatory system. Nerves of the rat gustatory system have limited capacity to regenerate if injured during neonatal ages but show robust recovery if the injury occurs in adulthood. Using this developmentally disparate model of regenerative capacity, we quantified microglia and astrocytes in the rostral nucleus of the solitary tract (rNTS) following transection of the gustatory chorda tympani nerve (CTX) of neonatal and adult rats. We found that neonatal CTX induced an attenuated microglia response but a larger astrocyte response compared to adult CTX. To elucidate the interplay between the microglia and astrocyte responses in the CTX model, we used our novel intraperitoneal injection protocol for the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia in the neonatal and adult rat brain prior to and after CTX. PLX5622 depleted microglia by 80–90% within 3 days of treatment, which increased to > 90% by 7 days. After 14 days of PLX5622 treatment, microglia were depleted by > 96% in both neonates and adults while preserving baseline astrocyte quantity. Microglia depletion eliminated the adult astrocyte response to CTX, while the neonatal astrocyte response after injury remained robust. Our results show injecting PLX5622 is a viable means to deplete microglia in neonatal and adult rats and suggest developmentally distinct mechanisms for astrogliosis following neural injury.
