Single-prolonged stress induced mitochondrial-dependent apoptosis in hippocampus in the rat model of post-traumatic stress disorder.
Post-traumatic stress disorder (PTSD) is a stress-related mental disorder caused by experience of a traumatic event, and presents with characteristic symptoms including intrusive memories, hyperarousal, and avoidance. Recently, structural neuroimaging studies showed that hippocampal volumes were relatively low in PTSD patients. However, the mechanisms that cause such atrophy are not well understood. The aim of this study was to reveal the possible mechanisms involved in apoptosis induced by single-prolonged stress (SPS) in hippocampus of PTSD rats. SPS is one of the animal models proposed for PTSD. Rats exposure to SPS showed enhanced inhibition of the hypothalamo-pituitary-adrenal (HPA) axis, which has been reliably reproduced in patients with PTSD. Wistar rats were killed at 1, 4, 7, 14 and 28 days after exposure to SPS. Expression of caspase-9, caspase-3, cytochrome c, Bcl-2 and Bax was detected by immunohistochemistry, immunofluorescence, Western blotting and electron microscopy. Apoptotic cells were assessed by TUNEL method. Our results showed apoptotic cells were significantly increased in hippocampus of SPS rats, accompanied by release of cytochrome c from the mitochondria into the cytosol, increase of caspase-9 and caspase-3 expression and decrease of the Bcl-2/Bax ratio. The results indicate that SPS-induced apoptosis in hippocampus of PTSD rats, and the mitochondrial pathway was involved in the process of SPS-induced apoptosis.
Li
Xiao Ming
XM
Department of Histology and Embryology, China Medical University, Shenyang, China.
Han
Fang
F
Liu
Dong Juan
DJ
Shi
Yu Xiu
YX
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000096:biosynthesis; D053453:Caspase 9 / Q000096:biosynthesis; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013313:Stress Disorders, Post-Traumatic / Q000473:pathology*; D013315:Stress, Psychological / Q000378:metabolism / Q000473:pathology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9