Evaluation of Hippocampal Allostatic Load-Associated Factors in Animal Models of Post-Traumatic Stress Disorder: Relevance to Human PTSD

Post-traumatic stress disorder is linked to higher allostatic load, nearly double the risk for metabolic syndrome, reduced hippocampal volume, and memory deficits. Using two rat models of PTSD, researchers found that predator odor stress caused conditioned place avoidance linked to reduced mitochondrial spare capacity and ROS production in the hippocampus. A separate chronic stress model increased cholesterol, triglycerides, and ROS production in the hippocampus. An experimental 5-HT2A agonist reduced ROS in the cortex and hippocampus and normalized gene expression overlapping with human PTSD. These findings support models connecting metabolic and allostatic features of PTSD to functional changes in the hippocampus.

Study at a glance

Abstract

Post-traumatic stress disorder (PTSD) is associated with elevated allostatic load, nearly double the risk for metabolic syndrome, reduced hippocampal volume, and contextual memory processing deficits. Emerging evidence suggests that these stress effects may predispose individuals to the development of PTSD, and there is a known relationship between chronic stress and metabolic dysfunction. In this work, we utilized two rat models of PTSD to explore these connections. We used an acute predator odor stressor to investigate the relationship between PTSD-like behaviors and mitochondrial dysfunction in the hippocampus of rats, and we observed that conditioned place avoidance was associated with reduced mitochondrial spare capacity and ROS production. In a separate multiple stressor + chronic psychosocial stress model, we observed increased cholesterol, triglycerides, and ROS production, fundamental allostatic load factors, in the hippocampus. In the same model, we also tested an experimental 5-HT2A agonist and known psychoplastogen and observed that it reduced ROS production in the cortex and hippocampus and normalized gene expression overlapping with human PTSD. Here, we show an association between mitochondrial dysfunction in the brain, the development of PTSD-like behaviors, and the induction of known allostatic load factors in the rat hippocampus after predator exposure + chronic psychosocial stress. Together these data support emerging models that suggest metabolic and allostatic characteristics of PTSD are related to functional changes in the hippocampus.