Neurogenesis and neurodegeneration in adolescent binge alcohol exposure

青少年酗酒中的神经发生和神经变性

• 批准号: 7387025
• 负责人: Kimberly Nixon
• 金额: $ 20.2万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-20 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7387025
• 关键词: Acute; Address; Adolescence; Adolescent; Adult; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcoholic Intoxication; Alcohols; Animal Model; Area; Behavioral; Birth; Blood alcohol level measurement; Brain; Brain Injuries; Cell Cycle; Cell Death; Cell Death Inhibition; Cell Differentiation process; Cell Proliferation; Cell Survival; Cells; Chemistry; Chronic; Cognitive deficits; Condition; Data; Diagnosis; Dose; Ethanol; Exploratory/Developmental Grant; Fibrinogen; Foundations; Future; Generations; Hippocampus (Brain); Human; Impairment; Individual; Modeling; Mosses; Nerve Degeneration; Neurons; Numbers; Population; Process; Public Health; Publishing; Rattus; Research; Rodent Model; Role; Solid; Stem cells; Structure; Students; Testing; Time; Tissues; Uridine; Work; alcohol effect; alcohol exposure; alcohol use disorder; base; binge drinker; binge drinking; cognitive function; cooking; dentate gyrus; experience; granule cell; high school; in vivo; killings; mature animal; migration; nerve stem cell; neurogenesis; neuron loss; neurophysiology; neuropsychological; novel; problem drinker; research study; underage drinking

DESCRIPTION (provided by applicant): Adolescence is a time when many individuals begin to experiment with alcohol. Alcohol abuse and alcohol dependence, collectively termed alcohol use disorders, are diagnosed in ~6% of adolescents and result in significant neuropsychological and/or cognitive deficits. As many as half of all high school students may currently drink alcohol and up to 70% of those students are binge drinkers. Considering that binge drinking is one of the factors that predicts brain damage from alcohol, understanding the impact of binge drinking on adolescent brain structure is an important public health concern. The neuroanatomical consequences of adolescent drinking are not well described, though two studies have shown hippocampal volume reductions in adolescents with alcohol use disorders. This finding confirmed behavioral and neurophysiological work in animal models that the adolescent hippocampus is targeted by alcohol. However, no one has examined whether alcohol directly produces neurodegeneration in the adolescent rat or the basic mechanism of cell or neuron reduction. The recent discovery that neural stem cells contribute to ongoing neurogenesis and to hippocampal structure suggests a novel potential mechanism of neurodegeneration alcohol-induced neurodegeneration. Thus, this application will test the overall hypothesis that binge alcohol exposure in the adolescent rat alters neural stem cells and neurogenesis to produce neurodegeneration. Three specific aims will address this hypothesis in an in vivo rat model of an adolescent alcohol use disorder by (1) investigating the effects of adolescent binge alcohol administration on the components of neurogenesis, (2) determining the mechanism by which alcohol intoxication inhibits neural stem cell proliferation and (3) evaluating whether changes in neurogenesis are associated with neurodegeneration (net reduction of cells) in the hippocampal dentate gyrus. Within each aim, important questions regarding the contribution of alcohol dose or duration necessary to alter the components of neurogenesis and the contribution of cell death will be investigated. Understanding the mechanism of alcohol-induced effects on neural stem cells and dentate gyrus granule cell loss forms a solid foundation to investigate the differential sensitivity of the adolescent brain to alcohol effects and the dynamic role of both cell death and cell birth mechanisms in neurodegeneration.

描述（由申请人提供）：青春期是许多人开始尝试酒精的时候。在约6％的青少年中诊断出酒精滥用和酒精依赖性，共同称为酒精使用障碍，并导致明显的神经心理学和/或认知缺陷。目前，多达一半的高中生可能会喝酒，其中多达70％的学生是暴饮暴食者。考虑到暴饮暴食是预测酒精脑损伤的因素之一，因此了解暴饮暴食对青少年大脑结构的影响是一个重要的公共健康问题。青少年饮酒的神经解剖学后果尚未得到很好的描述，尽管两项研究表明，饮酒障碍青少年的海马体积减少。这一发现证实了动物模型中的行为和神经生理学工作，即青少年海马是酒精针对的。但是，没有人检查酒精是直接在青少年大鼠中产生神经退行性的还是细胞或神经元还原的基本机制。最近的发现，神经干细胞有助于持续的神经发生和海马结构，这表明神经退行性醇诱导的一种新型的潜在机制 神经变性。因此，该应用将检验一个总体假设，即青少年大鼠中暴饮暴食的暴露会改变神经干细胞并产生神经变性。 Three specific aims will address this hypothesis in an in vivo rat model of an adolescent alcohol use disorder by (1) investigating the effects of adolescent binge alcohol administration on the components of neurogenesis, (2) determining the mechanism by which alcohol intoxication inhibits neural stem cell proliferation and (3) evaluating whether changes in neurogenesis are associated with neurodegeneration (net reduction of cells) in the hippocampal dentate回。在每个目标中，将研究有关改变神经发生成分所需的饮酒剂量或持续时间的重要问题以及细胞死亡的贡献。了解酒精诱导的对神经干细胞和齿状回颗粒细胞损失的作用的机制构成了研究青少年对酒精效应的差异敏感性以及细胞死亡和细胞出生机制在神经减退中的动态作用的稳定基础。