POWRE: Effects of Cytokines on Neuroendocrine Physiology

长期以来，人们一直认为压力，尤其是慢性压力，可以改变我们身体正常运作的方式。压力（生理和心理）改变各种免疫功能，这可能是将慢性压力与各种生理异常联系起来的重要因素。最近，科学家们对压力、免疫系统和大脑之间的相互作用产生了兴趣。越来越多的证据表明，压力可以刺激免疫细胞分泌化学物质（这些化学物质被称为细胞因子），而这些细胞因子反过来又可以改变特定的大脑功能。该power奖将研究免疫、神经内分泌和脑功能之间的关系。这个项目特别适合获得power奖，因为它将允许进行探索性工作，以确定Wayne博士的新探究线的可行性。这项工作的目的是研究细胞因子对脑细胞亚群功能的影响——神经内分泌细胞负责分泌一种控制生殖行为的激素。将使用一种具有简单神经系统的动物模型，即海洋软体动物。在拟议的研究中使用海雀的理由是，与大多数高等生物不同，海雀的神经内分泌细胞可以很容易地在活组织中识别出来。这意味着我们能够监测这些脑细胞对细胞因子的生理反应；我们可以测量它们对应激激活免疫细胞分泌的化学物质作出反应时的电和分泌活动的变化。此外，海洋无脊椎动物有一个功能类似于哺乳动物的原始免疫系统，包括细胞因子和与压力相关的激素，在结构上似乎与哺乳动物相似。本研究的目的是通过以下几个具体目标，将海兔的生殖神经内分泌细胞作为一个模型系统，以了解细胞因子，特别是白细胞介素和神经营养因子对膜兴奋性和下游神经内分泌细胞功能的影响：1)确定白细胞介素和神经营养因子对神经内分泌膜兴奋性和激素分泌的影响；2)确定白细胞介素和神经营养因子对海兔神经内分泌细胞激素mRNA水平和激素生物合成的影响。

It has long been suggested that stress, especially chronic stress, can alter the way in which our bodies normally function. Stress (both physiological and psychological) alters various immune functions, which could potentially be an important factor in linking chronic stress to a variety of physiological abnormalities. More recently, scientists have become interested in the interactions between stress, the immune system, and the brain. There is a growing body of evidence that stress can stimulate chemical secretions from immune cells (these chemicals are called cytokines), and that these cytokines can in turn alter specific brain functions. This POWRE award will investigate the relationship among immune, neuroendocrine and brain function. This project is particularly suited for a POWRE award because it will allow exploratory work to determine the feasibility of a new line of inquiry for Dr. Wayne. The purpose of the proposed work is to investigate the effects of cytokines on the function of a subset of cells from the brain - neuroendocrine cells that are responsible for secreting a hormone that controls reproductive behavior. An animal model with a simple nervous system, the marine mollusk Aplysia, will be used. The rationale for using Aplysia in the proposed studies is that, unlike with most higher organisms, their neuroendocrine cells can be easily identified in living tissue. That means that we are able to monitor the physiological response of these brain cells to cytokines; we can measure changes in both their electrical and secretory activities in response to chemicals that are secreted by stress-activated immune cells. Furthermore, marine invertebrates have a primitive immune system that is functionally analogous to that of mammals, including cytokines and stress-related hormones that appear to be structurally similar to their mammalian counterparts. The objective of this proposal is to develop the reproductive neuroendocrine cells of Aplysia as a model system to understand the effects of cytokines, and in particular interleukins and neurotrophins, on membrane excitability and downstream neuroendocrine cell functions by addressing the following specific aims: 1) determine the effects of interleukins and neurotrophins on neuroendocrine-membrane excitability and hormone secretion, and 2) determine the effects of interleukins and neurotrophins on hormone mRNA levels and hormone biosynthesis in Aplysia neuroendocrine cells.