Vol 83, No 2 (2024): Folia Morphologica
Original article
Published online: 2023-09-07
Oxidative stress mediates hippocampal neuronal apoptosis through ROS/JNK/P53 pathway in rats with PTSD triggered by high-voltage electrical burn
Abstract
Background: The pathogenesis of post-traumatic stress disorder (PTSD) triggered by high-voltage electrical burn (HVEB) remains unclear and the oxidative stress plays a role in this process. The purpose of this study is to investigate the underlying mechanism of oxidative stress mediates hippocampal neuronal apoptosis in rats with PTSD triggered by HVEB.
Materials and methods: The PTSD rat model was developed by stimulating with high voltage electricity and screened using behavioural performance including Morris water maze (MWM), elevated plus-maze (EPM) and open-field test (OFT). The reactive oxygen species (ROS) generation was measured by DHE fluorescence staining or flow cytometry. Western blotting assay was used to detect the proteins of p-JNK, JNK, P53, PUMA, Bcl-2 and Bax in hippocampal tissue or HT22 cells treated with electrical stimulation.
Results: The serum MDA and 8-OHdG levels were increased (p < 0.001), while the activities of SOD and CAT were decreased (p < 0.001) significantly in patients with HVEB. Behavioural test results showed that high-voltage electric stimulation induced the PTSD-like symptoms and the ROS-JNK-P53 pathway was involved in the neuronal apoptosis in rats with PTSD induced by HVEB. In vitro experiments further confirmed the electrical stimulation induced neuronal apoptosis through ROS/JNK/P53 signalling pathway and the antioxidant NAC could rescued the ROS generation, activation of JNK/P53 proteins and improved the cell apoptosis rate in HT22 cells. Finally, the JNK inhibitor SP600125 could significantly inhibited the percentage of HT22 cell apoptosis induced by electrical stimulation (p < 0.001).
Conclusions: These results indicated that oxidative stress mediates hippocampal neuronal apoptosis through ROS/JNK/P53 pathway in rats with PTSD triggered by HVEB.
Keywords: high voltage electric burnP53 proteinoxidative stressbrain injuryPTSD
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