Gender and Genetic effects on sleep:wake parameters following ethanol exposure

性别和遗传对睡眠的影响：乙醇暴露后的唤醒参数

• 批准号: 8119666
• 负责人: KRISTIN M HAMRE
• 金额: $ 17.79万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8119666
• 关键词: Address; Affect; Alcohol abuse; Alcohol dependence; Alcohol withdrawal syndrome; Alcoholism; Alcohols; Animal Model; Animals; Anxiety; Area; Behavioral Paradigm; Breathing; Characteristics; Chronic; Data; Electroencephalography; Ethanol; Exhibits; Future; Gender; Gender Role; Genes; Genetic; Genome; Goals; Human; Implant; Inbred Mouse; Inbred Strains Mice; Individual; Investments; Length; Measures; Mediating; Methods; Modification; Monitor; Motor Activity; Mouse Strains; Movement; Mus; Nature; Operative Surgical Procedures; Organism; Patients; Pattern; Phenotype; Physiological; Protocols documentation; Quantitative Trait Loci; Recombinant Inbred Strain; Recombinants; Relapse; Relative (related person); Respiration; Severities; Sleep; Sleep Wake Cycle; Sleep disturbances; Sleeplessness; Symptoms; System; Techniques; Testing; Time; Treatment outcome; Withdrawal; Withdrawal Symptom; Work; alcohol effect; alcohol exposure; design; improved; insight; interest; monitoring device; non rapid eye movement; novel; public health relevance; research study; response; sex; success; treatment program; treatment strategy; vapor

DESCRIPTION (provided by applicant): Withdrawal from chronic ethanol exposure results in a number of physiological responses. Two of those responses are altered sleep parameters and increased anxiety. However, little is known about either the factors that influence the severity of the alterations in sleep parameters or about whether there is a relationship between sleep: wake characteristics and anxiety during ethanol withdrawal. Two factors that have been shown to affect both sleep: wake characteristics and the severity of ethanol's withdrawal effects are the genetics or gender of the organism, and thus, the first experiment will test the hypotheses that genetics and/or gender or a combination of the two variables influences the severity of ethanol-induced changes in sleep. Testing of these hypotheses will be facilitated by the use of a novel system, the Piezo system, developed by the PI Dr. O'Hara. This system has the advantage of evaluating sleep patterns in a non-invasive fashion that also requires minimal labor investment. To test these hypotheses, DBA/2J (D2) and C57BL/6J (B6) mice as well as the BXD recombinant inbred mice generated by intercrossing the D2 and B6 mice will be examined. The addition of the BXD strains will allow us to not only address the hypotheses, but also to identify the region(s) of the genome that mediate any differential responses. Ethanol exposure will be given using vapor inhalation and following the multiple cycles of withdrawal and exposure of Veatch (2006), a technique that allows for the rapid induction of alcohol dependence. Comparisons of the sleep: wake parameters before ethanol exposure (baseline) will be compared to those during withdrawal. The second experiment will examine whether there is a relationship between the anxiety phenotypes of the animal and the severity of sleep alterations during ethanol withdrawal to determine whether the mice with the highest level of anxiety also show the most severe sleep disruptions during withdrawal. The anxiety phenotype of the mice will be addressed using several different behavioral paradigms including the elevated plus maze and locomotor activity in an activity chamber. Mice will be exposed to ethanol and the sleep: wake parameters monitored in the same manner as in the first experiment. Anxiety phenotypes will be assessed prior to ethanol exposure and during withdrawal. These experiments will provide insights into variables that need to be considered in the design of treatment programs for particular patients or in understanding the factors that mediate differences in treatment outcomes. PUBLIC HEALTH RELEVANCE: Sleep disruptions are one of the physiological responses that occur during alcohol withdrawal and have been shown to be a negative predictor of success in alcohol withdrawal. This proposal will provide insight into the role of gender and genetics in sleep disruptions following alcohol exposure and withdrawal as well as identify regions of the genome that underlie these differences.

描述（由申请人提供）：戒断长期接触乙醇会导致许多生理反应。其中两个反应是睡眠参数改变和焦虑增加。然而，对于影响睡眠参数变化严重程度的因素，或者睡眠：觉醒特征和乙醇戒断期间的焦虑之间是否存在关系，人们知之甚少。已证明影响睡眠的两个因素：觉醒特征和乙醇戒断效应的严重程度是生物体的遗传或性别，因此，第一个实验将检验遗传和/或性别或两者的组合的假设。有两个变量影响乙醇引起的睡眠变化的严重程度。 PI 博士 O'Hara 开发的压电系统这一新型系统的使用将有助于对这些假设进行测试。该系统的优点是以非侵入性方式评估睡眠模式，并且需要最少的劳动力投资。为了测试这些假设，将检查 DBA/2J (D2) 和 C57BL/6J (B6) 小鼠以及通过 D2 和 B6 小鼠杂交产生的 BXD 重组近交系小鼠。 BXD 菌株的添加不仅使我们能够解决假设，而且还能识别介导任何差异反应的基因组区域。乙醇暴露将通过蒸气吸入进行，并遵循 Veatch (2006) 的多次戒断和暴露循环，这是一种可以快速诱导酒精依赖的技术。睡眠比较：乙醇暴露前（基线）的唤醒参数将与戒断期间的参数进行比较。第二个实验将检查动物的焦虑表型与乙醇戒断期间睡眠改变的严重程度之间是否存在关系，以确定焦虑程度最高的小鼠在戒断期间是否也表现出最严重的睡眠中断。将使用几种不同的行为范例来解决小鼠的焦虑表型，包括高架十字迷宫和活动室中的运动活动。小鼠将接触乙醇，并以与第一个实验相同的方式监测睡眠：唤醒参数。将在乙醇暴露之前和戒断期间评估焦虑表型。这些实验将深入了解在为特定患者设计治疗方案或了解介导治疗结果差异的因素时需要考虑的变量。 公共卫生相关性：睡眠中断是戒酒过程中发生的生理反应之一，并且已被证明是戒酒成功的负面预测因素。该提案将深入了解性别和遗传学在酒精暴露和戒断后睡眠中断中的作用，并确定造成这些差异的基因组区域。