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Model of Fetal Alcohol Spectrum Disorder

胎儿酒精谱系障碍模型

基本信息

批准号：
10092876
负责人：
Sandra M Mooney
金额：
$ 36.83万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10092876
关键词：
Adolescence Adolescent Adult Anatomy Animals Attention Attentional deficit Autopsy Behavior Behavior Therapy Behavioral Biochemical Brain Brain region Cells Childhood Choline Clinical Cognition Cognitive Data Decision Making Development Dietary Intervention Dimensions Dose Ethanol Executive Dysfunction Experimental Designs Exposure to Female Fetal Alcohol Exposure Fetal Alcohol Spectrum Disorder Functional Magnetic Resonance Imaging Future Glutamates Grant Hippocampus (Brain)Human Hyperactivity Image Impairment Individual Information Storage Intellectual functioning disability Learning Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Memory Mind Modeling Morbidity - disease rate Morphology Neurons Nutritional Outcome Play Prefrontal Cortex Problem Solving Process Proteins Protons Rattus Reporting Rest Reversal Learning Rodent Model Role Sensory Short-Term Memory Structure Synapses System Testing Therapeutic Intervention Thinking Time Training alcohol effect alcohol exposure behavior test behavioral outcome choline supplementation cholinergic classical conditioning clinically relevant cognitive development critical period executive function experimental study flexibility frontal lobe gamma-Aminobutyric Acid improved improved outcome in vivo innovation interest learning ability male multidisciplinary neural circuit offspring postnatal prenatal prenatal exposure receptor response slow potential therapeutic development young adult

项目摘要

Fetal Alcohol Spectrum Disorder (FASD) is an umbrella term used to describe the range of outcomes that result from prenatal exposure to alcohol (ethanol). Behavioral effects may include hyperactivity, attention deficit, impaired sensory processing, and learning and memory problems. People with FASD may also have difficulties using information flexibly which likely underlies deficits in cognition. Such problems are thought to be seated in frontal cortices, including prefrontal cortex. Devising new strategies for amelioration of these problems has great clinical relevance. While deficits in learning and memory have been extensively demonstrated in rodent models of FASD, we will examine cognitive flexibility. We propose an innovative experimental design in which rats exposed to a moderate dose of ethanol prenatally are given choline AND behavioral training during adolescence. Either alone can improve learning and memory in normal animals, as well as in models of FASD. We have chosen the attentional set shifting and reversal learning task because it captures deficits reported in clinical observation of individuals with FASD and also because it can be used repeatedly in the same rats without observable diminution of responding or changes in task strategy. We propose a multidisciplinary set of experiments that will assess behavior, brain function and structure, as well as expression of neurometabolites. These experiments will determine whether modulating plasticity during frontal cortex development can improve both memory and problem solving in the same animals and how the effects manifest in brain connectivity and structure.

胎儿酒精谱系障碍（FASD）是一个总括性术语，用于描述胎儿酒精谱系障碍的范围。产前暴露于酒精（乙醇）的结果。行为影响可能包括多动症、注意力缺陷、感觉处理受损以及学习和记忆问题患有FASD的人也可能难以灵活地使用信息，是认知缺陷的基础这些问题被认为是位于额叶皮层，包括前额皮质制定新的战略来改善这些问题，临床相关性虽然学习和记忆的缺陷已被广泛证明， FASD的啮齿动物模型，我们将检查认知灵活性。我们提出了一个创新的实验设计中，大鼠产前暴露于中等剂量的乙醇，胆碱和青春期的行为训练。两者都可以提高学习效果，正常动物的记忆力，以及FASD模型。我们选择了注意力集中的转移和逆转学习任务，因为它捕捉了临床观察中报告的缺陷，也因为它可以在相同的大鼠中重复使用，可观察到的反应减少或任务策略的变化。我们提出了一个多学科的一系列实验，将评估行为，大脑功能和结构，以及表达神经代谢物这些实验将确定是否调节可塑性，额叶皮层的发展可以提高记忆力和解决问题的能力以及这些影响如何体现在大脑的连接和结构中。