OXIDATIVE DAMAGE, DNA, AND ETHANOL WITHDRAWAL

氧化损伤、DNA 和乙醇戒断

• 批准号: 7720891
• 负责人: MATTHEW J PICKLO
• 金额: $ 5.28万
• 依托单位: UNIVERSITY OF NORTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720891
• 关键词: Alcohol abuse; Alcohol consumption; Alcohol withdrawal syndrome; Alcoholic Intoxication; Aldehydes; Biochemical; Brain; Cerebral cortex; Cerebrum; Clinical; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Docosahexaenoic Acids; Emergency Situation; Funding; Glutathione; Goals; Grant; Hexenal; Hospitalization; Hyperactive behavior; Institution; Intervention; Life; Lipid Peroxidation; Lipids; Memory; Neurons; Performance; Polyunsaturated Fatty Acids; Rattus; Research; Research Personnel; Resources; Role; Seizures; Source; Testing; Toxic effect; United States National Institutes of Health; Withdrawal; Work; neurotoxic; peroxidation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Withdrawal from ethanol use poses unique clinical manifestations, including life-treatening seizures and hyperactivity that require emergency intervention and hospitalization. Multiple episodes of ethanol withdrawal are associated with poor memory performance, indicative of long-term CNS deficits. Ethanol withdrawal is associated with elevated oxidative damage to lipids in the brain. The long term goal of this work is to define the role of lipid peroxidation as neurotoxic sequelae of ethanol abuse and withdrawal. The objective of this proposal is to validate the extent to which peroxidation products of docosahexaenoic acid (DHA; 22:6, n-3) are elevated as a result of ethanol withdrawal. These data will be used for the development and assessment of better anti-withdrawal therapies and determining the biochemical mechanisms of toxicity. DHA is the most abundant polyunsaturated fatty acid in the brain and is concentrated in neuronal terminals. DHA has many important functions in the brain. Our initial data show that oxidative damage to DHA, assessed by F4-neuroprostanes (NeuroPs), occurs in the cerebral cortex of rats undergoing ethanol withdrawal. We demonstrate that trans-4-hydroxy-2-hexenal (HHE), a major unsaturated aldehyde product of DHA peroxidation, is toxic to rat cerebral cortical neurons and depletes neuronal glutathione. Our working hypothesis is that oxidative damage to DHA is elevated during the progression of ethanol withdrawal. This hypothesis will be tested through successful completion of the following aim: Define the progression of NeuroP and HHE formation as a result of ethanol intoxication and withdrawal.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 从乙醇使用中提取的提出构成了独特的临床表现，包括癫痫生命的癫痫发作和需要紧急干预和住院的多动症。 乙醇抽出的多个发作与记忆性能差有关，表明长期CNS缺陷。 乙醇抽出与大脑中脂质的氧化损伤升高有关。 这项工作的长期目标是将脂质过氧化作用定义为乙醇滥用和戒断的神经毒性后遗症的作用。 该提案的目的是验证二十二碳六烯酸的过氧化产物（DHA; 22：6，N-3）在多大程度上升高而导致乙醇撤离的结果。 这些数据将用于开发和评估更好的抗流水疗法，并确定毒性的生化机制。 DHA是大脑中最丰富的多不饱和脂肪酸，并集中在神经元末端。 DHA在大脑中具有许多重要的功能。 我们的最初数据表明，通过F4-神经前列腺（神经）评估的对DHA的氧化损伤发生在经受乙醇提取的大鼠的大脑皮层中。 我们证明了反式4-羟基-2-己酸（HHE）是DHA过氧化的主要不饱和醛产物，对大鼠脑皮质神经元和耗尽神经元谷胱甘肽有毒。 我们的工作假设是，在退出乙醇的过程​​中，对DHA的氧化损害升高。 该假设将通过成功完成以下目的来检验：定义神经和HHE形成的进展，这是由于乙醇中毒和戒断而导致的。