Does Nitric Oxide Control Synaptic Zinc Release?

一氧化氮是否控制突触锌的释放？

• 批准号: 6547753
• 负责人: CHRISTOPHER J. FREDERICKSON
• 金额: $ 14.84万
• 依托单位: NEUROBIOTEX, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-23 至 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6547753
• 关键词: charge coupled device camera; electrical measurement; electrodes; fluorescence microscopy; fluorescent dye /probe; genetically modified animals; hippocampus; injection /infusion; laboratory mouse; laboratory rat; microdialysis; nerve injury; neural degeneration; neurotoxicology; nitric oxide; synapses; zinc

DESCRIPTION (provided by applicant): Synaptically-released zinc has toxic impact in seizure, ischemia, and trauma, contributing to neuronal injury in all three conditions. Conversely, blockade of the excitotoxic synaptic zinc flux with zinc chelators can reduce neuronal degeneration markers by as much as 80%. We have recently discovered evidence indicating that Nitric Oxide (NO) may control the synaptic release of zinc. Should NO prove to be the controlling factor, this would open completely new avenues for management of zinc-induced brain damage in stroke, ischemia, trauma, and seizure. Moreover, prophylactic control of the Zn2+ toxicity via NO modulation could be used as therapeutic pretreatment in cardiac bypass and carotid endarterectomy procedures. Our pilot data indicate that NO infused into the brain simultaneously depletes presynaptic boutons of their zinc while releasing zinc into dialysates, and we have complementary data from brain slice preparations indicating that NO causes the release of Zn2+ into the bath. Perhaps more compelling, additional data suggest that zinc-induced neuronal injury after head trauma is decreased by up to 50% after blockade of NO* synthesis. The objective of the present proposal is to establish with certainty whether, in fact, NO controls Zn2+ release during excitotoxicity.

描述（由申请人提供）：突触发行的锌对癫痫发作，缺血和创伤都有毒性影响，在所有三种情况下都会导致神经元损伤。相反，用锌螯合剂阻断兴奋性突触锌通量可以将神经元变性标记降低多达80％。 我们最近发现的证据表明一氧化氮（NO）可以控制锌的突触释放。如果没有证明是控制因素，这将为管理中风，缺血，创伤和癫痫发作的脑部损伤提供全新的途径。此外，通过无调节对Zn2+毒性的预防控制可以用作心脏搭桥和颈动脉内膜切除术中的治疗预处理。 我们的飞行员数据表明​​，在将锌释放到透析液中的同时，没有注入大脑的脑突触前胸子，我们有来自脑切片制剂的互补数据，表明没有导致Zn2+释放到浴室中。也许更引人注目的是，其他数据表明，锌诱导的头部创伤后神经元损伤在封闭无*合成后降低了50％。本提案的目的是确定在兴奋性毒性期间是否没有控制Zn2+释放。