Neuropeptide/Microglial Interactions That Ensure Brain Homeostatis

如果说神经元是大脑功能的“业务端”，那么神经胶质细胞就是支持人员。神经元和神经胶质细胞之间的动态平衡相互作用为大脑的最佳运作提供了健康的环境。这项研究探索了一种类型的神经元-神经胶质相互作用-多肽神经递质和小胶质细胞之间的相互作用。小胶质细胞驻留在大脑中，能够对感染、神经退行性疾病或中枢神经系统损伤做出促炎反应。它们也可以作为常驻的抗原提呈细胞，我们之前NSF资助的数据表明，它们还可以产生促进未成熟神经元存活和/或分化的生长因子。神经肽--特别是血管活性肠肽(VIP)、垂体腺苷环化酶激活肽(PACAP)和甘丙素--似乎在调节小胶质细胞的反应性中发挥作用。我们的初步数据显示，这三种神经肽都有抑制炎症反应的作用，可能是通过不同的机制。对这些细胞内机制的探索是该项目一个目标的重点。另一个目标是确定VIP和PACAP调节小胶质细胞抗原提呈能力的潜在机制。该项目的最终目标是确定神经肽--特别是甘丙素--在调节小胶质细胞生长因子的产生和神经元发育中所起的作用。

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.