Adult neurobiology following adolescent drinking

描述（由申请人提供）：奖励、情感和行为控制的成熟与从青春期到成年期的过渡期间额叶皮层和边缘脑区域的形态变化相吻合。青少年时期饮酒非常普遍，但其对成熟的影响目前尚不清楚。我们实验室以前的研究表明，青春期大鼠对乙醇诱导的神经变性和海马神经发生的抑制比成年大鼠更敏感。青少年酒精暴露在小鼠中被证明减少前脑体积和基底核中的胆碱能细胞群，这与Morris水迷宫上的逆转学习障碍有关。虽然酗酒在青春期很常见，但酒精暴露是否会导致大脑形态的持续变化尚不清楚。此外，尚不清楚青春期酗酒是否会增加成年后患精神病理学的可能性。这个博士后奖学金资助假设青少年间歇性乙醇（AIE）将持续改变额叶皮层和边缘系统的细胞和形态成熟，这将最终改变成人的认知和情感功能。AIE范例将用于以下3个目标：目标1。检验AIE诱导青少年大脑形态持续变化并持续到成年的假设。目标2.测试青少年间歇性乙醇（AIE）暴露改变青少年和成人脑细胞组成和神经发生的假设。目标3.检验青少年间歇性乙醇（AIE）将导致神经认知功能改变的假设，这种改变在成年后将是明显的。 AIE处理后，将使用神经成像评估青少年（P56）和成年（P80）大鼠的脑完整性、皮质厚度、白色物质束和局部体积（Aim 1）。将进行免疫组织化学，以评估青少年和成人脑神经元/神经胶质组成和神经发生（目的2）。将对暴露于AIE的成年大鼠进行认知测量（巴恩斯迷宫、空间和反向学习）或情绪行为组合（强迫游泳、旷场、社会互动、高架十字迷宫[Aim 3]）评估。创新的培训方法，其中涉及神经影像学（Styner和Oguz），免疫组织化学（Crews）和行为评估（Crews）领域专家的指导和指导，以及参加课程和研讨会，将允许深入评估青少年酗酒对成年后大脑成熟和功能的有害影响。事实上，青少年饮酒后行为、形态和脑组织学的持续改变可能会改变人们对未成年饮酒的态度，并发现成人脑病理学和精神疾病的新病因机制。

DESCRIPTION (provided by applicant): Maturation of reward, affect, and behavioral control coincides with morphological changes in the frontal cortex and limbic brain regions during the transition from adolescence to adulthood. Alcohol consumption during adolescence is highly prevalent, but its impact on maturation is currently unknown. Previous studies from our laboratory have shown that adolescent rats are far more sensitive to ethanol-induced neurodegeneration and inhibition of hippocampal neurogenesis than adults. Adolescent binge ethanol exposure in mice was demonstrated to reduce forebrain volume and cholinergic cell populations in the nucleus basalis that was associated with reversal learning impairment on the Morris Water maze. Although binge drinking is common during adolescence, it is unknown whether alcohol exposure results in persistent changes to brain morphology. Furthermore, it is unknown if binge drinking during adolescence increases the likelihood of developing psychopathology in adulthood. This Postdoctoral Fellowship grant hypothesizes that adolescent intermittent ethanol (AIE) will persistently alter both cellular and morphological maturation of th frontal cortex and limbic system, which will culminate in altered adult cognitive and emotive function. The AIE paradigm will be used in the following 3 Aims: Aim 1. Test the hypothesis that AIE induces persistent changes to adolescent brain morphology that continue into adulthood. Aim 2. Test the hypothesis that adolescent intermittent ethanol (AIE) exposure alters adolescent and adult brain cellular composition and neurogenesis. Aim 3. Test the hypothesis that adolescent intermittent ethanol (AIE) will result in alterations to neurocognitive function that wil be evident in adulthood. Following AIE treatment, neuroimaging will be used to assess brain integrity, cortical thickness, white matter tracts, and regional volumes in adolescent (P56) and adult (P80) rats (Aim 1). Immunohistochemistry will be performed to assess adolescent and adult brain neuronal/glial composition and neurogenesis (Aim 2). Adult rats exposed to AIE will be assessed on a measure of cognition (Barnes maze, spatial and reversal learning) or an emotive behavioral battery (forced swim, open-field, social interaction, elevated plus-maze [Aim3]). The innovative training approach, which involves guidance and instruction from experts in the field of neuroimaging (Styner and Oguz), immunohistochemistry (Crews), and behavioral assessment (Crews) as well as attendance of courses and seminars, will allow for an in depth assessment of the detrimental effects of adolescent alcohol abuse on brain maturation and function in adulthood. Indeed, persistent alterations in behavior, morphology, and brain histology following adolescent alcohol exposure could change attitudes regarding underage drinking and discover new etiological mechanisms of adult brain pathology and mental illness.