Neuropeptide/Microglial Interactions That Ensure Brain Homeostatis

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If neurons are the "business end" of brain function, glia comprise the support staff. Homeostatic interactions between neurons and glia provide the healthy environment in which the brain functions best. This research explores one type neuronal-glial interaction - that between peptide neurotransmitters and microglia. Microglial cells reside in brain and are capable of a pro-inflammatory response to infection, neurodegenerative disease, or CNS trauma. They can also serve as resident antigen-presenting cells, and data from our previous NSF funding suggests that they also produce growth factors that promote survival and/or differentiation of immature neurons. Neuropeptides -- specifically vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide (PACAP) and galanin - seem to play a role in regulating microglial responsiveness. Our preliminary data show that all three neuropeptides serve to dampen the inflammatory response, possibly by different mechanisms. An exploration of these intracellular mechanisms is the focus of one goal of the project. Another goal is to determine the mechanism underlying the means by which VIP and PACAP modulate microglial antigen-presenting capability. The final goal of the project is to determine the role that neuropeptides - specifically galanin - play in regulating microglial growth factor production and, hence, neuronal development.