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Original article
Submitted: 2023-05-28
Accepted: 2023-08-21
Published online: 2023-09-07
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Oxidative stress mediates hippocampal neuronal apoptosis through ROS/JNK/P53 pathway in rats with PTSD triggered by high-voltage electrical burn

Ying Lv12, Xuegang Zhao3, Rui Zhang3, Zhaopeng He1, Yanfeng Xu1, Lihong Tu1, Lei Jiang3, Shunjiang Xu3, Qingfu Zhang1
·
Pubmed: 37691512
Affiliations
  1. Department of Burns and Plastic Surgery, the First Hospital of Hebei Medical University, Shijiazhuang, China
  2. Department of Cardiac Surgery, the First Hospital of Hebei Medical University, Shijiazhuang, China
  3. Hebei Key Laboratory of Brain Science and Psychiatric-Psychologic Disease, Shijiazhuang, China

open access

Ahead of Print
ORIGINAL ARTICLES
Submitted: 2023-05-28
Accepted: 2023-08-21
Published online: 2023-09-07

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 behavioral 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. Behavioral 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 signaling 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.

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 behavioral 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. Behavioral 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 signaling 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.

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Keywords

high voltage electric burn, P53 protein, oxidative stress, brain injury, PTSD

About this article
Title

Oxidative stress mediates hippocampal neuronal apoptosis through ROS/JNK/P53 pathway in rats with PTSD triggered by high-voltage electrical burn

Journal

Folia Morphologica

Issue

Ahead of Print

Article type

Original article

Published online

2023-09-07

Page views

350

Article views/downloads

340

DOI

10.5603/fm.95727

Pubmed

37691512

Keywords

high voltage electric burn
P53 protein
oxidative stress
brain injury
PTSD

Authors

Ying Lv
Xuegang Zhao
Rui Zhang
Zhaopeng He
Yanfeng Xu
Lihong Tu
Lei Jiang
Shunjiang Xu
Qingfu Zhang

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