Thermoprotected mechanisms regulating neurotransmitter release following heat pre

热保护后调节神经递质释放的热保护机制

• 批准号: 7296494
• 负责人: SHANKER KARUNANITHI
• 金额: $ 7.55万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7296494
• 关键词: Acute; Anoxia; Attenuated; Behavior; Binding; Body Temperature; Cells; Chromosome Pairing; Clinical; Condition; Cytosol; Daily; Docking; Drosophila genus; Electron Microscopy; Electrophysiology (science); Exocytosis; Exposure to; Fever; Future; Glutamates; Heat Stroke; Heat shock proteins; Heat-Shock Proteins 70; Heating; High temperature of physical object; Homeostasis; Hypertension; Investigation; Ischemia; Knowledge; Lead; Life; Mammals; Molecular Chaperones; Nervous system structure; Organism; Physiological; Presynaptic Terminals; Production; Proteins; Recruitment Activity; Site; Stress; Stroke; Synapses; Temperature; Testing; Vesicle; Work; clinically relevant; genetic manipulation; hyperthermia treatment; neurotransmitter release; prevent; protein function; research study; size; stem; stressor; synaptic function; therapy development

DESCRIPTION (provided by applicant): Synapses are critical sites of information transfer within the nervous system. Therefore, if synapses incur stress-induced damage, behaviors required for daily living would be severely compromised. Homeostatic mechanisms can be recruited to maintain synaptic function under adverse conditions through prior exposure to mild stress. However, the underlying mechanisms are poorly understood. We previously showed that malfunction of Drosophila glutamatergic synapses at high temperatures can be attenuated by heat pretreatment (brief exposure to sublethal temperatures). Major heat shock proteins (HSPs) upregulated by heat pretreatment are found to be partly responsible for conferring synaptic thermoprotection. In spite of this knowledge, the key synaptic mechanisms and/or proteins thermoprotected by heat shock proteins are unknown. The specific aim of this proposal is: to elucidate which mechanisms of evoked transmitter release are thermoprotected at elevated temperatures by heat pretreatment. Future investigations stemming from these pilot experiments will allow us to identify key synaptic proteins associated with the thermoprotected mechanisms chaperoned by HSPs. This in turn will allow us to determine how HSPs interact with synaptic proteins to maintain synaptic homeostasis under stress. We seek to identify mechanisms regulating neurotransmitter release that are protected from failing at high temperatures by heat pretreatment. The general findings of our investigations will ultimately lead to the development of therapies to prevent stress-induced synaptic damage.

描述（由申请人提供）：突触是神经系统中信息传输的关键站点。因此，如果突触引起的压力引起的损害，日常生活所需的行为将受到严重损害。可以通过事先暴露于轻度压力来招募稳态机制以在不利条件下维持突触功能。但是，基本机制知之甚少。我们先前表明，在高温下，果蝇谷氨酸能突触的故障可能会通过热预处理（短暂暴露于每日的温度）来减弱。发现由热预处理上调的主要热休克蛋白（HSP）是赋予突触热保护的部分原因。尽管有这些知识，但未知的热休克蛋白热保护的关键突触机制和/或蛋白质尚不清楚。该提案的具体目的是：阐明在高温下通过热预处理在升高的温度下对哪些诱发发射机释放的机制进行热保护。这些试验实验的未来研究将使我们能够鉴定与HSP伴随热保护机制相关的关键突触蛋白。反过来，这将使我们能够确定HSP如何与突触蛋白相互作用以在压力下保持突触稳态。我们试图确定调节神经递质释放的机制，这些机制可保护通过热预处理在高温下损坏。我们调查的一般发现最终将导致开发疗法，以防止压力引起的突触损伤。