Overactivation of LPS-stimulated microglial cells by co-cultured neurons or neuron-conditioned medium.

Microglial activation represents a well known aspect of several neuropathological diseases. However, little is known concerning the role of neurons in starting and modulating this process. In the present report, we demonstrate that differentiated, healthy neurons constitutively release in the culture medium substance(s) that are able to induce a state of overactivation in LPS-stimulated microglial cells. The neuronal factors synergize with LPS in stimulating synthesis and release of interleukin-1beta (IL-1beta) and nitric oxide by microglial cells. Prolonged exposure (72 h) to neuron-conditioned media in the presence of LPS induced microglial apoptosis, thus suggesting that neuronal overactivation of stimulated microglia favors their subsequent apoptotic elimination as part of a safety mechanism.