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

University Of California Los Angeles, Los Angeles CA

Investigators

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Abstract

Abstract 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 sensitivity 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.