Neuron-microglia interactions in vitro.

We observed that soluble factor(s) in microglia-conditioned medium supported the survival of cerebral cortical neurons from E15 mouse in a dose-dependent manner. In mixed neuron-microglia cultures, neurons possessed long neurites with extensive arborization and could survive for up to 4 weeks. In such cultures, neurons had an up-regulated level of phosphotyrosine immunoreactivity as compared to those in pure neuron cultures. In mixed cultures, microglia extended cytoplasmic processes toward the growing neurites, and when they contacted neurites, the microglia changed morphology by flattening and rounding up by extending thin cytoplasmic processes. Microglia survived longer in mixed cultures than in pure microglia cultures, with or without neuron-conditioned medium. Under all these culture conditions, microglia were phagocytic as evaluated by Fc receptor-mediated phagocytosis of opsinized sheep erythrocytes, suggesting that the phagocytic activity of microglia does not impair their capacity to support neuronal survival. However, lipopolysaccharide treated microglia did impede neuronal survival in mixed cultures. These observations indicate that, in vitro, microglia can be either neurotrophic or neurotoxic depending upon the microenvironment. The mixed neuron-microglia cultures described provide a valuable in vitro model systems for studying the direct interactions between neurons and microglia.