Non-Human Primate Model for Systems Biology Studies of Stress Response

用于应激反应系统生物学研究的非人类灵长类动物模型

基本信息

批准号：
8903979
负责人：
Anna Joanna Jasinska
金额：
$ 15.09万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8903979
关键词：
Abbreviations Acute Adolescent Affect Animal Model Animals Behavior Behavioral Biochemical Biochemical Process Biocompatible Materials Biological Biological Models Biomedical Research Brain Cardiovascular system Caribbean region Cataloging Catalogs Cercopithecus tantalus Chronic Disease Cognition Cognitive Complex Disease Exposure to Foundations Future Gene Expression Gene Expression Profile Gene Expression Profiling Genes Genetic Genetic Variation Genomics Global Change Health Housing Human Hypothalamic structure Immune Immunity Individual Individual Differences Infectious Agent Inflammation Inflammatory Response Intervention Investigation Island Link Measurable Measures Mediating Mediator of activation protein Mental disorders Metabolic Metabolism Modeling Molecular Molecular Profiling Neurosecretory Systems Organ Pathway Analysis Phenotype Physiological Physiology Pituitary Gland Population Predisposition Procedures Psychological Stress Psychosocial Stress Quarantine RNA Sequences Research Research Personnel Resources Risk Risk Factors Rodent Sampling Social isolation Source Stress System Systems Biology Tissues Transcript Variant Weight acute stress addiction base behavioral response biological adaptation to stress body system cardiometabolic risk cognitive testing differential expression gene discovery genetic association genetic variant genome sequencing genome-wide insight model development nonhuman primate novel marker pleiotropism psychological stressor psychosocial repository response stressor trait transcriptome sequencing transcriptomics vervet

项目摘要

DESCRIPTION (provided by applicant): Behavioral and physiological responses to psychosocial stressors can predict the long-term health consequences of exposure to stress. These consequences include dramatically elevated risks for cardiometabolic diseases, addictions, and mental disorders. Little is known, however, about either the genetic variation underlying inter-individual variation in susceptibility to stress, or about the gene expression patterns that provide the presumed mechanism for such variation. We propose to create, using the Caribbean vervet monkey (Chlorocebus aethiops sabaeus), a translational non-human primate (NHP) model for stress responsivity studies, which will facilitate investigations of the multi-system effects of an acute psychosocial stressor on physiology, behavior and cognition. These investigations are not feasible in humans, and cannot be reliably modeled in rodents, which differ from humans too substantially in these systems. We will leverage the short-term quarantine procedures applied routinely to wild-trapped vervets on the island of St. Kitts to investigate multi-system measures hypothesized to be associated with stress-responsivity. Specifically, we will longitudinally monitor expression of genes and gene networks that are stress-regulated and that predict individual differences in behavioral and physiological sensitivit to stress. This proof of concept study will validate the proposed model by: 1) demonstrating the impact of the stressor on metabolic, inflammatory and behavioral responses; 2) characterizing inter-individual variations in stress-related traits; 3) showing mechanistic links between stress-induced changes in higher-order phenotypes and gene expression patterns. Development of this model will, in the short-term provide insights into the molecular underpinnings of stress- related diseases, and, in the long-term, pave the way for large scale genetic and genomic investigations to identify the basis for individual differences in response to stress.

描述（由申请人提供）：对社会心理压力源的行为和生理反应可以预测承受压力的长期健康后果。这些后果包括对心脏代谢疾病，成瘾和精神障碍的风险急剧升高。然而，关于压力敏感性的个体间变异或基因表达模式的基因表达模式，鲜为人知的遗传变异是提供了这种变异的假定机制。我们建议使用加勒比海肉猴（Chlorocebus aethiops sabaeus）创建一种转化的非人类灵长类动物（NHP）模型，以进行压力反应性研究，这将促进对急性心理压力对物理学，行为和认知的多系统影响的研究。这些研究在人类中是不可行的，不能在啮齿动物中可靠地建模，在这些系统中，这些研究与人类的不同。我们将利用通常应用于圣基茨岛上野生捕获的天线的短期隔离程序来研究被认为与压力响应率有关的多系统测量。具体而言，我们将纵向监测应力调节的基因和基因网络的表达，并预测行为和生理敏感性对压力的个体差异。该概念研究证明将通过以下方式验证所提出的模型：1）证明应激源对代谢，炎症和行为反应的影响； 2）表征与压力相关性状的个体间变化； 3）显示应力诱导的高阶表型变化与基因表达模式之间的机械联系。在短期内，该模型的发展将提供有关压力相关疾病的分子基础的见解，并且从长远来看，为大规模的遗传和基因组研究铺平了道路，以确定对压力响应的个体差异的基础。