Neuroinflammation, Neuronal IL-1R1, and Behavior

项目摘要 神经炎症是包括神经退行性疾病在内的大多数中枢神经系统疾病的重要因素 疾病和心理障碍。神经炎症的一个特征是血管内皮生长因子表达增加 脑组织中的促炎细胞因子白介素1(IL-1)。IL-1是如何引起神经和精神疾病的 人们对病理学知之甚少。我们最近发现，IL-1的受体IL-1R1是 在大脑中特定的神经元组中表达。这些神经元IL-1R1，即nIL-1R1，调节神经元 通过非规范信号通路改变神经元功能和电路连接的活动。这 应用程序旨在：1)绘制nIL-1R1在大脑中的分布，2)显示参与 NIL-1R1在神经炎性行为障碍和神经病理中的作用，以及3)阐明 NIL-1R1介导的神经调节机制。

Project Summary Neuroinflammation is a significant contributor to most CNS disorders including neurodegenerative diseases and psychological disorders. A hallmark of neuroinflammation is the increased expression of the proinflammatory cytokine interleukin-1 (IL-1) in the brain. How IL-1 causes neuro- and psycho- pathologies is poorly understood. We have recently discovered that the receptor for IL-1, IL-1R1, is expressed in specific sets of neurons in the brain. These neuronal IL-1R1s, nIL-1R1, modulate neuronal activity via non-canonical signaling pathways to alter neuronal function and circuit connectivity. This application is designed to: 1) map nIL-1R1 distribution in the brain, 2)demonstrate the involvement of nIL-1R1 in neuroinflammation induced behavioral deficits and neuropathology, and 3) elucidate the mechanisms of nIL-1R1 mediated neuromodulation.