Releasing factors from mature neurons modulate microglial survival via purinergic receptor activation

Activated microglia release many types of substances to neurons. However, little is known concerning how information from neurons is received by microglia prior to the induction of these substances. Here, we examined whether neurons modulate microglial function. Treatment with conditioned medium of mature cerebellar granule neurons (CGCs) and cortical neurons significantly induced the death of lipopolysaccharide (LPS)-stimulated microglia. On the other hand, treatment with conditioned medium of mature superior ganglion neurons induced microglial cell death in neither the presence nor absence of LPS. Conditioned medium of mature CGCs induced nuclear condensation. In contrast, treatment with heat-treated conditioned medium or low-calcium ion medium prevented the death of LPS-stimulated microglia. Pretreatment with P2X7 agonist enhanced microglial cell death in neither the presence nor absence of LPS. These findings suggest that unknown pyrolytic releasing factors of brain-derived mature neurons influence microglial survival.