PTSD and apoptosis

Post-traumatic stress disorder (PTSD) is a disorder related to trauma that can develop after exposure to serious harm or threat of serious harm. PTSD may stimulate the affected individual to re-experience and react to the experience for years. Many studies have linked PTSD to impaired hippocampal function, citing a correlated decrease in hippocampal volume in those affected. This volume depression has been associated with apoptosis in the hippocampus.

Apoptosis is the genetically controlled response of cells to intrinsic and environmental factors that results in the orderly and clean destruction of unorthodox cells.

Many intrinsic pathways for apoptosis have been studied including activation of the defensive response by the endoplasmic reticulum (ER). The ER is an intracellular organelle charged with the synthesis and maturation of the cell surface, maintenance of Ca++ homeostasis, and secretion of proteins. Disrupted ER function can induce accumulation of unfolded proteins and the subsequent unfolded protein response (UPR). Prolonged stress to the ER leads to UPR initiated apoptotic cell death. This pathway is supported by the UPR induced change in molecular chaperone (GRP$78$‍) production. In response to a single-prolonged-stress (SPS), GRP$78$‍ expression is initially increased to protect the ER against apoptosis, but if the ER is unable to find reprieve from the stress, as is the case in the recurrent stress of PTSD, GRP$78$‍ expression begins to decline signaling the induction of the apoptotic pathway.

This phenomenon can be seen in Figure $1$‍, which highlights GRP$78$‍ decline beginning $4$‍ days after termination of the single prolonged stress in rats with PTSD.

FIgure $1$‍