An orchestrating role of mitochondria in the origin and development of post-traumatic stress disorder

Abstract

Post-traumatic stress disorder (PTSD) is one of the most discussed and actively researched areas in medicine, psychiatry, neurophysiology, biochemistry and rehabilitation over the last decades. Multiple causes can trigger post-traumatic stress disorder. Humans subjected to violence, participants in hostilities, victims of terrorist attacks, physical or psychological persecution, witnessing scenes of cruelty, survival of natural disasters, and more, can strongly affect both children and adults. Pathological features of post-traumatic stress disorder that are manifested at molecular, cellular and whole-organism levels must be clearly understood for successful diagnosis, management, and minimizing of long-term outcomes associated with post-traumatic stress disorder. This article summarizes existing data on different post-traumatic stress disorder causes and symptoms, as well as effects on homeostasis, genetic instability, behavior, neurohumoral balance, and personal psychic stability. In particular, we highlight a key role of mitochondria and oxidative stress development in the severity and treatment of post-traumatic stress disorder. Excessive or prolonged exposure to traumatic factors can cause irreversible mitochondrial damage, leading to cell death. This review underlines the exceptional importance of data integration about the mechanisms and functions of the mitochondrial stress response to develop a three-dimensional picture of post-traumatic stress disorder pathophysiology and develop a comprehensive, universal, multifaceted, and effective strategy of managing or treatment post-traumatic stress disorder.

Keywords: glucocorticoids; inflammation; mitochondria; post-traumatic stress disorder; reactive oxygen species.

FIGURE 1

Physiological changes during post-traumatic stress disorder (PTSD). Following the traumatic event, PTSD is common and is one of the serious health concerns. PTSD can be associated with lasting changes in the brain areas implicated in the stress response include the amygdala, hippocampus, and prefrontal cortex. Functional limitations and respiratory syndromes may co-ocuure with PTSD. Stress is also the major risk factor for cardiovascular disease (CVD). Pathophysiology includes changes in the immune system function in individuals with PTSD suggest its association with enhanced immune inflammatory activity.

FIGURE 2

Mitochondrial response to PTSD. The hypothalamic–pituitary–adrenal (HPA) axis is the primary neuroendocrine pathway involved in stress response via release of secretions (A). Glucocorticoids appear to regulate mitochondrial transcription. Mitochondrial stress response includes changes in mitochondrial dynamics, retrograde signaling, the mitochondrial unfolded protein response (UPR_mt), selective autophagy of mitochondria (mitophagy), or apoptotic cell death (B). Stress results in synaptic release of glutamate and binding to NMDA receptor that leads to calcium influx. Ca²⁺ overload results in collapse of mitochondrial membrane potential (ΔΨm), decrease in ATP production, and enhanced ROS generation (C).