Alcohol and Development of the Prefrontal Cortex

酒精与前额皮质的发育

• 批准号: 7755831
• 负责人: Leon Garland Coleman
• 金额: $ 2.95万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-09 至 2012-09-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7755831
• 关键词: Acute; Adolescence; Adolescent; Adult; Aftercare; Age; Alcohol abuse; Alcohol dependence; Alcoholism; Alcohols; Anxiety; Apoptosis; Architecture; Area; Behavior; Behavioral; Biological; Brain; Brain imaging; Brain region; Cell Death; Cell physiology; Cells; Cellular Structures; Cerebrum; Complex; Development; Developmental Process; Dysmorphology; Environment; Ethanol; Ethanol toxicity; Growth; Histocytochemistry; Hour; Human; Inflammation; Intelligence; Interneurons; Lead; Learning; Life; MK801; Magnetic Resonance Imaging; Mus; N-Methylaspartate; Neurons; Parvalbumins; Pathology; Pharmacotherapy; Prefrontal Cortex; Prevention; Public Health; Pyramidal Cells; Reversal Learning; Risk; Short-Term Memory; Silver Staining; Staging; Stress; Structure; Synapses; Techniques; Testing; Time; Toxic effect; Visual Cortex; Weight; Youth; adolescent alcohol abuse; adolescent alcohol exposure; adolescent binge drinking; alcohol effect; alcohol exposure; alcohol sensitivity; base; binge drinking; caspase-3; critical period; fetal; frontal lobe; gamma-Aminobutyric Acid; hippocampal pyramidal neuron; mature animal; neurochemistry; neurotoxic; postnatal; prenatal; prepulse inhibition; underage drinking

DESCRIPTION (provided by applicant): The developing brain is uniquely sensitive to insults, including ethanol. Although fetal brain development and alcohol toxicity have been extensively studied, early postnatal and adolescent stages of cerebral cortical brain development have not been extensively studied. "Critical periods" of unique high environment regulated plasticity occurs for many brain regions with the most studied being visual cortex. During these "critical periods of plasticity", developmental processes result in the formation of persisting synaptic and other cytoarchitecture and cellular function. Human alcohol abuse during adolescence and young adulthood is associated with an increased risk of alcoholism in adulthood. Thus the overall hypothesis is that alcohol abuse during post-natal periods of brain development will cause acute toxicity that results in persistent alterations to adult brain cortical cells and results in persistent changes in adult behavior and adult gross brain structure. This proposal will investigate the effects of ethanol exposure during distinct periods of early postnatal life and adolescence on cellular and synaptic architecture, behavior, and gross brain structure in adult animals. The frontal cortex will be targeted due to its late development and sensitivity to ethanol toxicity. The three specific aims of this project and their associated techniques are as follows: 1. to histochemically determine the effects of ethanol on post-natal days (PND) 7 and 14 as well as through adolescence (PND28-38) on cell death markers (activated caspase 3 and silver stain) just after treatment; and to examine adult frontal cortical structure following prenatal treatment using neuron specific markers for GABA interneurons and pyramidal cells; 2. to determine the effects of early postnatal and adolescent ethanol on adult behaviors, including tests of working memory, learning and reversal learning, prepulse inhibition, and anxiety; and 3. to determine the effects of ethanol during the early postnatal and adolescent periods on gross brain structure using Magnetic Resonance Imaging (MRI). Magnetic resonance imaging in humans has found continued development of cortical regions into the 3rd decade of life. Mouse brain development during this period has not been well studied, although neurochemical and behavioral studies have suggested similar courses of brain development between humans and mice; although the timing is clearly different. Using structural MRI we will test the effects of early postnatal and adolescent exposure of ethanol on adult brain regional volumes. Human adolescents commonly binge drink, and adolescent drinking is associated with increased risk of alcoholism. If it is established that the adolescent brain has unique vulnerability this could lead to increased prevention and treatment of adolescent binge drinking.

描述（由申请人提供）：发育中的大脑对包括乙醇在内的侮辱非常敏感。尽管已经对胎儿脑发育和酒精毒性进行了广泛的研究，但尚未对脑皮质脑发育的早期和青春期阶段进行广泛的研究。独特的高环境调节可塑性的“关键时期”发生在许多大脑区域，其中最多的是视觉皮层。在这些“可塑性的关键时期”中，发展过程导致形成持续的突触和其他细胞结构和细胞功能。青春期和成年时期的人类酗酒与成年后酗酒的风险增加有关。因此，总体假设是，在产后大脑发育期间的酗酒会导致急性毒性，从而导致对成人脑皮质细胞的持续改变，并导致成人行为和成人脑结构的持续变化。该建议将研究乙醇在产后早期生活和青春期不同时期对成年动物中细胞和突触结构，行为和大脑结构的影响。 额叶皮层由于其较晚的发育和对乙醇毒性的敏感性而成为目标。该项目及其相关技术的三个具体目的如下：1。在组织化学上确定乙醇对产后日（PND）7和14的影响以及通过青春期（PND28-38）（PND28-38）对细胞死亡标记（Acivated Caspase 3和Acivated Caspase 3和Silver STAIN）的影响；并在产前治疗后使用神经元特异性标记来检查成年额叶结构，用于GABA中间神经元和金字塔细胞； 2。确定早期产后和青少年乙醇对成人行为的影响，包括工作记忆，学习和逆转学习的测试，抑制和焦虑； 3。使用磁共振成像（MRI）确定乙醇在产后和青少年早期对脑结构的影响。人类中的磁共振成像发现皮质区域持续发展到生命的第三个十年。尽管神经化学和行为研究表明人与小鼠之间的大脑发育类似，但在此期间的小鼠脑发育尚未得到很好的研究。虽然时机明显不同。使用结构MRI，我们将测试乙醇早期和青少年暴露对成年脑区域体积的影响。人类青少年通常是暴饮暴食，青少年饮酒与酗酒风险增加有关。如果确定青少年大脑具有独特的脆弱性，这可能会导致预防和治疗青少年暴饮暴食。