Astrocyte branchlet dysfunction as an early step in brain disorders

星形胶质细胞分支功能障碍是脑部疾病的早期步骤

• 批准号: 9334301
• 负责人: Baljit Khakh
• 金额: $ 77万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-26 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9334301
• 关键词: Astrocytes; Award; Brain; Brain Diseases; Brain Injuries; Budgets; Corpus striatum structure; Data; Disease; Excision; Functional disorder; Glues; Goals; Lead; Maintenance; Mental disorders; Neurobiology; Neurodevelopmental Disorder; Neurons; Neurosciences; Neurotransmitters; Outcome; Physiology; Process; Regulation; Review Committee; Role; Signal Transduction; Synapses; Synaptic Transmission; Testing; Vertebrates; Withdrawal; Work; excitotoxicity; nervous system disorder; novel; novel therapeutics; operation; public health relevance

DESCRIPTION (provided by applicant): A central goal of neurobiology is to understand how the brain forms, stores, retrieves and encodes information and how these operations go awry in disease. The focus of this application is astrocytes, which make intimate contacts with neurons throughout the brain. Long considered simply the brain's glue, astrocytes are emerging as important regulators of neuronal function. Deciphering the roles of astrocytes in the brain is considered one of the major open questions in neuroscience. This Pioneer Award application seeks to test the novel hypothesis that an early step in brain disorders involves dysfunction of the very fine termini of astrocytes called branchlets that are known to abut synapses. In this context, we define dysfunction as branchlet withdrawal from synapses or altered branchlet signaling, including trophic support, to synapses. These dysfunctions would alter established astrocyte functions including neurotransmitter clearance, synapse regulation and maintenance. This in turn would alter the timing of synaptic transmission, contribute to excitotoxicity and perhaps trigger synapse removal. By focusing on the striatal microcircuitry, we will test the hypothesis that branchlets represents a hitherto overlooked mechanism in neurological and psychiatric disorders that could be exploited for novel therapeutics.

描述（由申请人提供）：神经生物学的一个中心目标是了解大脑如何形成，存储，检索和编码信息，以及这些操作如何在疾病中出错。这种应用的重点是星形胶质细胞，它与整个大脑的神经元密切接触。长期以来，星形胶质细胞被认为是大脑的粘合剂，现在正成为神经元功能的重要调节者。破译星形胶质细胞在大脑中的作用被认为是神经科学中的主要开放问题之一。这项先锋奖申请旨在测试一种新的假设，即大脑疾病的早期阶段涉及星形胶质细胞非常精细的末端功能障碍，称为小枝，已知与突触相邻。在这种情况下，我们将功能障碍定义为从突触撤回的小枝或改变的小枝信号传导，包括营养支持，突触。这些功能障碍将改变已建立的星形胶质细胞功能，包括神经递质清除，突触调节和维护。这反过来又会改变突触传递的时间，导致兴奋性毒性，并可能触发突触移除。通过专注于纹状体微电路，我们将测试的假设，即小枝代表一个迄今为止被忽视的机制，在神经和精神疾病，可以利用新的治疗方法。