Prostaglandin E2 (PGE2) is an eicosanoid that mediates microglial activity via two PGE2 receptor subtypes expressed by microglia, EP1 and EP2. EP2 receptor activation has been shown to be neuroprotective but whether this effect involves microglia has not been examined. EP2 enhances macrophage recycling endocytosis, a process now known to be involved in TNF- secretion, which can trigger neuroprotection. Our laboratory’ s work shows that treatment of microglia with monomeric IgG triggers neuroprotection via TNF- involving recycling endocytosis. Therefore, we asked whether EP2 receptor activation might enhance IgG-based neuroprotection via increased recycling endocytosis and TNF- production in microglia. Hippocampal organotypic culture slices were pretreated with EP2 agonist Butaprost, Butaprost + IgG, or vehicle for three days and then injured with NMDA to reveal the neuroprotective effects of each treatment. In separate experiments, primary microglia were cultured and the degree of recycling endocytosis measured via semi-quantitative immunostaining for RAB11, a marker of endocytosis, after treatment with Butaprost, and Butaprost + IgG. It is expected that EP2 activation with Butaprost will enhance the neuroprotective effects of IgG via increased recycling endocytosis and the resultant release of TNF- This suggests for the first time that signals from increased physiological neural activity may trigger neuroprotection via benign activation of microglia immune signaling.
Wade Swenson, ’07 Brooklyn Park, MN
Major: Biochemistry and Molecular Biology
Sponsor: Barbara Christie-Pope