Lipid-like components released from degenerating dopaminergic neurons trigger the dynamic migration of microglia

Abstract

In the brain, communication between neural and non-neural cells is crucial for the proper functioning of the central nervous system. Microglia play an important role in the clearance of neural cellular corpses and debris, especially under pathological conditions. It remains, however, unclear how microglia sense the degenerating neurons at a distance in order to migrate to them. In the present study, we explored the interaction between neurons and microglia using an in vitro model of Parkinson’s disease (PD). In primary mesencephalic neuronal cultures, 1-methyl-4-phenylpridinium (MPP+) induced the selective death of dopaminergic (DAergic) neurons in a dose- and time-dependent manner. Transmigration assay showed that the conditioned medium (CM) from mesencephalic cultures treated with MPP+ was enough to trigger the attraction of microglia at an early as well as a late phase of neuronal damage. Microglia preferably reacted with the soluble parts separated by ultracentrifugation over the neural debris-containing pellets. This chemoattractive activity was significantly reduced by the removal of the lipidic components in CM, but not by the removal of proteins, DNA or RNA. These results suggest that as yet-unidentified lipid-like components released from dying DAergic neurons are likely to recruit microglia, and thus have a role in neuronal damage.