1/2 NADIA U24 Dendritic Spine Core

1/2 NADIA U24 树突脊柱核心

基本信息

批准号：
9026909
负责人：
PATRICK J. MULHOLLAND
金额：
$ 16.82万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9026909
关键词：
Adolescence Adolescent Adult Affect Alcohol consumption Alcohols Amygdaloid structure Award Axon Behavior Behavioral Brain Brain region Cell Communication Characteristics Cognition Cognitive Complex Cyclic AMP Data Dendritic Spines Development Developmental Process Environment Epigenetic Process Exposure to Glutamate Receptor Hippocampus (Brain)Human Impairment Laboratories Learning Medial Memory Morphology N-Methylaspartate Neurons Neurosciences Performance Phenotype Physiology Plastics Prefrontal Cortex Prevalence Process Public Health Publishing Research Research Personnel Risk Rodent Shapes Signal Transduction Signaling Protein Site Sleep Structure Synapses Testing Vertebral column adolescent alcohol exposure alcohol exposure alcohol use disorder brain cell cognitive task density emerging adult functional adaptation gray matter high risk high risk drinking neuroadaptation neurobehavioral neuromechanism public health relevance social anxiety underage drinking white matter

项目摘要

DESCRIPTION (provided by applicant): Alcohol use disorders are a major public health issue and emerging evidence suggests that high-risk drinking during adolescence has long-term consequences on behavior and brain development. The brain undergoes profound structural and functional adaptations throughout adolescence, and some critical brain regions even continue to mature into early adulthood. Over the last few years, studies published from the NADIA Consortium and other laboratories showed that adolescent intermittent alcohol (AIE) exposure produces profound behavioral, cognitive, electrophysiological, and neuroanatomical impairments that persist in adult rodents. The underlying neuroadaptations that contribute to the persistent consequences of high-risk adolescent drinking remain largely unknown. Three components of the NADIA Consortium found that AIE exposure alters dendritic spine density and morphology in the adult amygdala (Pandey component), prefrontal cortex (Chandler component), and hippocampus (Swartzwelder component). An analysis of the morphological characteristics of spines revealed that AIE exposure selectively increased the prevalence of `immature' long, thin dendritic spines in the adult prefrontal cortex and hippocampus. Previous findings suggest that maturation of asymmetric synapses during the natural process of developmental pruning involves replacing immature synapses associated with long, thin spines with mature synapses associated with mushroom-shaped dendritic spines. Thus, AIE exposure appears to impair the normal maturation of synaptic pruning in the adult brain. Because dendritic spine morphology influences synaptic physiology and behavior, aberrant structural plasticity of neurons in the adult brain is a likely neural mechanism underlying deficits in cognition and behavior associated with AIE exposure. The convergence of these findings prompted the formation of a NADIA Dendritic Spine Core that will integrate dendritic spines changes in multiple brain regions induced by AIE exposure. The overarching hypothesis of this NADIA Dendritic Spine Core is that AIE exposure locks-in an adolescent morphological phenotype in the adult brain that diverges from the normal pruning process. The purpose of this Core is to provide a detailed analysis of dendritic spine density and spine morphology in brain regions relevant to the behavioral, electrophysiological, and epigenetic studies of the NADIA Consortium. The Dendritic Spine Core will provide analysis of dendritic spine changes in a primary and secondary brain region for each NADIA component. This Core will also characterize developmental changes in dendritic spine density and morphology in brain regions related to the NADIA Consortium components. The data provided to the NADIA Consortium by this Core on the impact of AIE exposure on dendritic spine adaptations and the developmental trajectory of spine morphology will influence the neuroscience field and inform public health.

描述（由申请人提供）：酒精使用障碍是一个主要的公共卫生问题，新的证据表明，青春期的高风险饮酒会对行为和大脑发育产生长期影响。大脑在整个青春期经历深刻的结构和功能适应。一些关键的大脑区域甚至持续成熟到成年早期，NADIA 联盟和其他实验室发表的研究表明，青少年间歇性酒精（AIE）暴露会对行为、认知、电生理和行为产生深远的影响。成年啮齿类动物中持续存在的神经解剖学损伤导致高风险青少年饮酒的持续后果的潜在神经适应仍然很大程度上未知。 NADIA 联盟的三个组成部分发现，AIE 暴露会改变成年杏仁核的树突棘密度和形态。）、前额皮质（Chandler 成分）和海马体（Swartzwelder 成分）对棘的形态特征的分析表明，AIE 选择性暴露。成人前额皮质和海马中“不成熟”的长而细的树突棘的患病率增加，先前的研究表明，在发育修剪的自然过程中，不对称突触的成熟涉及用与长而细的树突棘相关的成熟突触取代与长而细的树突棘相关的不成熟突触。因此，AIE 暴露似乎会损害成人大脑中突触修剪的正常成熟。脊柱形态影响突触生理和行为，成人大脑中神经元的异常结构可塑性可能是与 AIE 暴露相关的认知和行为缺陷的潜在神经机制，这些发现的融合促进了 NADIA 树突脊柱核心的形成，该核心将整合。 AIE 暴露引起多个大脑区域的树突棘变化 NADIA 树突棘核心的总体假设是 AIE 暴露锁定了成人的青少年形态表型。该核心的目的是提供与 NADIA 联盟的行为、电生理学和表观遗传学研究相关的大脑区域的树突棘密度和树突棘形态的详细分析。提供每个 NADIA 组件的初级和次级大脑区域的树突棘变化分析。该核心还将表征与 NADIA 联盟相关的大脑区域的树突棘密度和形态的发育变化。该核心向 NADIA 联盟提供的有关 AIE 暴露对树突棘适应的影响以及树突棘形态发育轨迹的数据将影响神经科学领域并为公众健康提供信息。