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

• 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
• 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

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）：对心理社会压力源的行为和生理反应可以预测暴露于压力的长期健康后果。这些后果包括心脏代谢疾病、成瘾和精神障碍的风险急剧增加。然而，很少有人知道，无论是遗传变异的个体间差异的易感性压力，或有关的基因表达模式，提供这种变化的假定机制。我们建议创建，使用加勒比海长尾猴（Chlorocebus aethiops sabaeus），翻译非人灵长类动物（NHP）模型的压力反应性研究，这将有助于调查的多系统影响的急性心理社会应激对生理，行为和认知。这些研究在人类中是不可行的，并且不能在啮齿动物中可靠地建模，啮齿动物在这些系统中与人类的差异太大。我们将利用短期的检疫程序，定期应用于野生诱捕的长尾小蠹在圣基茨岛调查多系统的措施，假设与压力反应。具体来说，我们将纵向监测基因和基因网络的表达，压力调节和预测个体差异的行为和生理敏感性的压力。该概念验证研究将通过以下方式验证所提出的模型：1）证明压力对代谢，炎症和行为反应的影响; 2）表征压力相关性状的个体间差异; 3）显示压力诱导的高阶表型和基因表达模式变化之间的机制联系。该模型的开发将在短期内提供对压力相关疾病的分子基础的见解，并且从长期来看，为大规模遗传和基因组研究铺平道路，以确定对压力的个体差异的基础。