Cytokine neurotransmitter interactions and sleep

描述（申请人的摘要）：中枢神经系统（CNS）和免疫系统 系统进行相互通信。睡眠是中枢神经系统的基本过程 由神经递质调节并对免疫挑战作出反应， 我们生病时睡眠的变化就是明证。本申请中 我们专注于5-羟色胺（5-HT） 和白细胞介素-1（IL-1）作为神经递质的代表， 参与睡眠调节的免疫活性分子。我们之前 研究了IL-1对5-HT的作用，并显示对IL-1的睡眠反应是 如果5-HT系统被拮抗，则改变。本申请中提出的研究 注重相互作用，即，5-HT对IL-1的影响我们的中央 一种假说认为，促睡眠细胞因子能激活促睡眠细胞因子 IL-1可能是5-HT发挥作用的因素之一， 睡吧这一中心假设将在本报告的框架内加以讨论。 以下问题。1)肾上腺素能激活是否改变脑IL-1 系统？2)当大脑IL-1系统被激活时，5-HT对睡眠的影响是否会改变 敌对？3)视前区/下丘脑前部（POA）是一个重要的 这些互动的网站？这些问题将使用 行为、电生理和分子方法。我们的初步 来自大鼠的数据表明多巴胺能激活增加NREM睡眠， 下丘脑IL-1 mRNA表达和c-fos活性。这些新结果 而之前的研究表明， 系统在功能上与睡眠相关。5-HT和IL-1参与了这一过程。 调节多种生理功能， 除了睡眠之外的行为。因此，虽然我们的重点仍然是坚定地 睡眠，我们提出的综合实验方法将导致 与基础和临床神经科学的几个领域相关的信息。

DESCRIPTION (Applicant's Abstract): The central nervous system (CNS) and immune system engage in reciprocal communication. Sleep is a fundamental CNS process that is regulated by neurotransmitters and responds to immune challenge, as evidenced by changes in sleep that occur when we are sick. In this application we focus on interactions in brain between serotonin (5-hydroxytryptamine; 5-HT) and interleukin-1 (IL-1) as representatives of neurotransmitters and immune-active molecules that are involved in sleep regulation. We previously investigated IL-1 effects on 5-HT and showed that sleep responses to IL-1 are altered if the 5-HT system is antagonized. Studies proposed in this application focus on the reciprocal interaction, i.e., 5-HT effects on IL-1. Our central hypothesis is that, serotonergic activation stimulates the somnogenic cytokine IL-1, which may be one of the factors through which 5-HT exerts its effects on sleep. This central hypothesis will be addressed within the framework of the following questions. 1) Does serotonergic activation alter the brain IL-1 system? 2) Are 5-HT effects on sleep altered when the brain IL-1 system is antagonized? 3) Is the preoptic area/anterior hypothalamus (POA) an important site for these interactions? These questions will be addressed using behavioral, electrophysiological, and molecular approaches. Our preliminary data from the rat indicate that serotonergic activation increases NREM sleep, IL-1 mRNA expression, and c-fos activity in the hypothalamus. These new results and those of previous studies indicate that interactions between these two systems are functionally relevant to sleep. 5-HT and IL-1 are involved in the regulation in the regulation of a number of physiological functions and behaviors in addition to sleep. As such, although our focus remains firmly on sleep, the integrated experimental approach we propose will result in information relevant to several fields of basic and clinical neuroscience.