Wild-derived zebrafish as models for anxiety and stress responsiveness

野生斑马鱼作为焦虑和压力反应模型

基本信息

批准号：
8264749
负责人：
JOHN R GODWIN
金额：
$ 18.3万
依托单位：
NORTH CAROLINA STATE UNIVERSITY RALEIGH
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-05-20 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8264749
关键词：
Address Adult Animal Model Animals Anxiety Anxiety Disorders Architecture Behavior Behavioral Biological Models Brain Breeding Candidate Disease Gene Complex Development Diagnosis Disease Economic Burden Environment Exhibits Family Study Female Fishes Follow-Up Studies Future Gene Expression Gene Expression Profile Genes Genetic Genome Genome Scan Genomics Genotype Goals Human India Individual Laboratories Lead Modeling Molecular Profiling Mood Disorders Morbidity - disease rate Neurobiology Organism Parents Phenotype Population Prevalence Public Health Relative (related person)Research Research Project Grants Resources Rewards Risk Screening procedure Sex Characteristics Sexual Maturation Staging Stress System Testing Time Translating Twin Studies Variant Work Zebrafish base coping coping mechanism design developmental genetics experience gene discovery hatching high throughput screening innovation insight male model development mortality neuromechanism neuropsychiatry programs public health relevance relating to nervous system sex success transcriptomics

项目摘要

DESCRIPTION (provided by applicant): Anxiety disorders are among the leading causes of illness in the U.S., yet their origins and the way in which an individual's genotype interacts with the environment to influence disease remain poorly understood. The long-term goal of these studies is to better understand the genetic and neurobiological underpinnings of variation in anxiety and stress-responsiveness. This work will employ the zebrafish model, but with an innovative focus on fish recently derived from wild stocks. The value of these wild-derived individuals is in the heightened levels and greater variation in anxiety-related behaviors they display relative to an established laboratory stocks. The specific goals of this exploratory project are first to compare gene expression profiles in the brains of two wild-derived zebrafish lines divergent in the display of anxiety-related behavior (high and low respectively) to two established laboratory lines that also show behavioral variation. The wild-derived zebrafish lines exhibit what have been termed 'proactive' and 'reactive' coping styles in other model systems and also pronounced sex differences with females exhibiting higher levels of anxiety-related behavior. The second goal of these studies is to compare gene expression profiles in the brain between the two divergent wild-derived lines at time points ranging from early development until after maturation when sex differences in anxiety-related behaviors have emerged. The goal of this second aim is to begin exploring the developmental origins of coping style differences in adulthood. The benefits of this project should include behavioral and neurogenomic characterization of a zebrafish model system that will lead to mechanistic studies in zebrafish and potentially studies of identified candidate genes in human association studies. The zebrafish model system is also particularly well suited to studying the genomic and developmental underpinnings of anxiety-related behaviors and the ways in which these mechanisms are influenced by an organism's environment. PUBLIC HEALTH RELEVANCE: This project addresses the genetic and developmental origins of anxiety-related behaviors using the zebrafish as a model system. Anxiety disorders are prevalent and therefore represent a significant public health issue imposing significant illness and economic burdens on the U.S. population.

描述（由申请人提供）：焦虑症是美国疾病的主要原因之一，但它们的起源以及个人的基因型与环境相互作用以影响疾病的方式仍然很少了解。这些研究的长期目标是更好地了解焦虑和压力反应性变异的遗传和神经生物学基础。这项工作将采用斑马鱼模型，但具有创新的重点，这些焦点是最近源自野生股票的鱼。这些野生衍生的个体的价值是它们相对于已建立的实验室库存而显示的与焦虑有关的行为的水平更高，并且焦虑相关行为的差异更大。该探索性项目的具体目标首先将两个野生衍生的斑马鱼线在显示焦虑相关行为（高和低较低）的两种野生衍生斑马线线的大脑中比较基因表达谱，并比较出表现出行为变化的两个已建立的实验室线。野生衍生的斑马鱼线在其他模型系统中表现出所谓的“主动”和“反应性”应对方式，并且在女性中表现出更高水平与焦虑相关的行为的性别差异。这些研究的第二个目标是在两个不同的野生衍生线之间比较大脑中的基因表达谱，从早期发育到成熟之后，与焦虑相关行为的性别差异发生了。第二个目标的目的是开始探索成年后应对风格差异的发展起源。该项目的好处应包括斑马鱼模型系统的行为和神经基础表征，该系统将在人类关联研究中导致斑马鱼的机械研究以及对鉴定候选基因的潜在研究。斑马鱼模型系统也特别适合研究与焦虑相关行为的基因组和发育基础以及这些机制受生物环境影响的方式。公共卫生相关性：该项目解决了使用斑马鱼作为模型系统的焦虑相关行为的遗传和发育起源。焦虑症很普遍，因此代表了一个重大的公共卫生问题，对美国人群造成了重大疾病和经济负担。