POPULATION-CONTROL OF MICROGLIA - DOES APOPTOSIS PLAY A ROLE

Brain lesions, even of the most subtle type, are accompanied by the ac tivation of microglia, the main immune cells of the brain. Microglial cells dramatically increase in number through proliferation and adhere to the injured neurons, where they displace the synaptic input. After proliferation, microglia gradually migrate into the nearby parenchyma and appear to decrease in number. Here we examined the possible invol vement of apoptosis in the regulation of the microglial cell number us ing Terminal transferase mediated d-UTP Nick End-Labelling (TUNEL). In vitro, cell death is a common phenomenon in microglial cell cultures, and is enhanced by the withdrawal of the mitogen, granulocyte-macroph age colony stimulating factor. In vivo, application of the TUNEL-react ion revealed TUNEL-positive microglia beginning at day 4, with a peak 7 days after transection of the facial nerve. Surprisingly, TUNEL-labe lling in vivo was localized on the outer side of the nuclear membrane and in the microglial cytoplasm, with very little staining within the nucleus itself. These TUNEL-labelled cells also lacked other classic m orphological signs of apoptosis, like membrane blebbing, chromatin con densation and apoptotic bodies. These data suggest that the regulation of post-mitotic microglia is not mediated by the classic pathway of a poptosis.