MPP+-induced COX-2 activation and subsequent dopaminergic neurodegeneration

SPECIFIC AIMSThe purpose of this study was to determine whether in an in vitro Parkinson’s disease (PD) model 1) microglia participate in MPP+-induced COX-2 activation and 2) the activation of COX-2 contributes to subsequent dopaminergic neurotoxicity. A series of experiments using mouse primary mesencephalic neuron-glia cultures and related reconstitution studies were performed to delineate the underlying mechanisms of the COX-2 activation in MPP+-treated neuron-glia cultures.PRINCIPAL FINDINGS1. Microglia are necessary for MPP+-induced PGE2 production in primary neuron-glia culturesTo determine whether microglia are necessary for MPP+-induced PGE2 production in neuron-glia cultures, different cultures including enriched neuron, enriched microglia, and mixed neuron-microglia cultures were treated with 0.1–0.5 μM MPP+ and levels of released PGE2 were determined after 4 days. As shown in Fig. 1⤻ A, MPP+ treatment significantly increased PGE2 production in mixed neuron-microglia cultures, in a dose-dependen...