Changes of Bax, Bcl-2 and apoptosis in hippocampus in the rat model of post-traumatic stress disorder

Published by Maney Publishing (c) W. S. Maney & Son Limited Objective: Post-traumatic stress disorder (PTSD) is a stress-related mental disorder caused by experience of a traumatic event. PTSD is often accompanied by morphological and functional changes in the hippocampus. Recently, it was reported that the hippocampal volumes of PTSD patients are relatively low. However, the mechanisms that cause such atrophy are not well understood. Single prolonged stress (SPS) is one of the animal models proposed for PTSD. The aim of this study was to reveal whether hippocampal neuronal apoptosis and the expression of apoptosis-related protein and gene occur and investigate behavioral and electrophysiological changes of hippocampi in SPS rats. Methods: Wistar rats were killed at 1, 4, 7, 14 and 28 days after exposure to SPS. The apoptotic cells were assessed by TUNEL method and transmission electron microscopy. Bax and Bcl-2 expression was detected by immunohistochemistry, immunofluorescence, western blotting and RT-PCR. Behavioral and electrophysiological alterations were detected by Morris water maze test and long-term potentiation (LTP) respectively. Results: Our results showed that apoptosis exactly occurred in hippocampus of SPS rats. Apoptotic cells reached peak level at 7 days after exposure to SPS. Both Bcl-2 and Bax were significantly up-regulated during early PTSD. Bcl-2 reached peak level at 4 days. Bax reached peak level at 7 days. Behavioral analyses revealed that the SPS rats exhibited obvious impaired spatial memory that paralleled the deficits in hippocampal LTP. Conclusion: In conclusion, SPS caused a series of morphological and behavioral changes in hippocampus. Apoptosis may be one of the reasons inducing hippocampus atrophy. The changes of apoptosis-related proteins and genes of Bcl-2 and Bax might be involved in the early molecular regulatory mechanism of apoptosis in PTSD. The impaired LTP was related to apoptosis in the hippocampus of SPS rats. The mechanisms of apoptosis and impaired LTP might be involved in PTSD.