Neuroinflammation, Neuronal IL-1R1, and Behavior

神经炎症、神经元 IL-1R1 和行为

• 批准号: 10373034
• 负责人: Ning Quan
• 金额: $ 34.22万
• 依托单位: FLORIDA ATLANTIC UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10373034
• 关键词: Acute Brain Injuries; Adhesions; Aging; Anatomy; Animal Model; Atlases; Behavior; Behavioral; Binding; Brain; CNS autoimmune disease; Cells; Central Nervous System Diseases; Chronic; Data; Development; Disease; Epilepsy; Etiology; Genetic Polymorphism; Genetic Predisposition to Disease; Glutamates; Hippocampus (Brain); Human Genetics; Impaired cognition; Inflammatory; Interleukin-1; Interleukin-1 Receptors; Knock-in; Knock-in Mouse; Label; Light; Link; LoxP-flanked allele; Maps; Mediating; Memory impairment; Mental disorders; Methods; Microscopy; Modeling; Molecular; Mood Disorders; Mus; Nervous system structure; Neurodegenerative Disorders; Neurologic; Neurons; Neurotransmitters; Pathogenesis; Pathology; Pathway interactions; Predisposition; Protein Tyrosine Phosphatase; Reporter; Role; Short-Term Memory; Signal Pathway; Signal Transduction; Stress; Synapses; System; Tracer; Withdrawal; behavioral study; cell type; comorbidity; cytokine; design; fighting; mRNA Expression; neuroinflammation; neuropathology; neuroregulation; novel; prevent; protein expression; psychologic; receptive field; receptor; receptor expression; response; single cell sequencing; social; synaptogenesis

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.

项目摘要 神经炎症是大多数中枢神经系统疾病（包括神经退行性疾病）的重要原因 疾病和心理障碍。神经炎症的一个标志是神经细胞膜上的 促炎细胞因子白细胞介素-1（IL-1）在大脑中的作用。IL-1是如何引起神经和精神疾病的 病理学知之甚少。我们最近发现IL-1的受体IL-1 R1， 在大脑中特定的神经元中表达。这些神经元IL-1 R1，nIL-1 R1，调节神经元 通过非经典信号传导途径改变神经元功能和电路连接的活性。这 该应用程序被设计为：1）映射nIL-1 R1在大脑中的分布，2）证明参与 nIL-1 R1在神经炎症诱导的行为缺陷和神经病理学中的作用，以及3）阐明 nIL-1 R1介导的神经调节机制。