Abstract

Multinucleated Microglia are formed in response to aging, inflammation, the presence of some pathogens, and are a histological feature of several CNS pathologies. Multinucleated microglia may be involved with increased clearance of CNS debris and whole cells. The present study has sought to determine the best model by which to study multinucleation in microglia in vitro, in order to investigate whether the known neurotoxicant metal lead (Pb) impacts the formation of multinucleated microglia. It was determined that isolated rat microglia (Sprague-Dawley), compared to murine (BV2) and human (HMC3) microglia cell-lines, when induced by Phorbol-myristate-acetate (PMA) results in the greatest amount of cell multinucleation and multinuclearity. In this model, it was shown that long-term exposure to Pb inhibited microglia cell proliferation, multinucleation, and multinuclearity in a dose-dependent manner. Pb appears to inhibit multinucleation in microglia by induction of multinuclear regression (karyolysis, pyknosis, or karyorrhexis) resulting in large mononuclear cells. The mechanism by which PMA induces multinucleation may involve p38/MAPK activity and Pb interferes with this activation.