The long-term consequences of exposure to adverse experience on muscle physiology

Abstract

Physical inactivity is a growing burden among society and is especially prominent in groups with psychological trauma including adverse childhood experiences (ACEs) and post-traumatic stress disorder (PTSD). The prevalence of ACEs and PTSD are high across society and can considerably increase the risk of developing the deadliest chronic diseases through elevated inflammation, oxidative stress, and disruptions in energy balance. The sedentary lifestyle can contribute to the same maladaptive physiological states and chronic diseases risk as ACEs and PTSD, and thus may be a mediating factor. However, it is currently not clear how exposures to adverse experiences may disrupt biological processes in manners that contribute to persistent physical inactivity. This thesis will detail some findings in rats on how exposure to adverse experiences might generate persistent maladaptive responses to muscle physiology that could contribute to persistent physical activity deficits. To that end, young adult male rats were exposed to a single episode of uncontrollable tail shocks (Stress, N=12) or left undisturbed in home cages (No Stress, N=12). Forty-eight hours later, half of the rats from each stress condition received free access to running wheels (Running) or remained in cages without running wheels (Sedentary) for 42 days. At the conclusion of the study, gastrocnemius muscle was taken, and Western Blots were utilized to measure protein biomarkers of inflammation, oxidative stress, and energy balance among the rats including HSP70, SIRT1, TNF-a, AMPk and total pAMPK, and IL-6. Results show that stress exposure caused a 4-fold decreased in wheel running distance that persisted for the entire 42-day access to wheels. Stress-induced deficits in wheel running were associated with a trend towards elevated TNF-a and lowered IL-6 in the gastrocnemius muscle. These data suggest exposure to adverse experience may generate persistent changes to inflammatory factors in muscle that may chronically impair physical activity output. Future studies are required for a more complete analysis of the immunological pathways involved, as it could be of central importance to understanding the development of sedentary lifestyles following exposure to adverse events.