Abstract
In an animal model of post-traumatic stress disorder (PTSD), our previous studies showed mitochondrial stress-induced apoptosis in the hippocampus. Metformin, the most commonly prescribed anti-diabetic drug, exerts its effects through 5′-adenosine monophosphate-activated protein kinase (AMPK) activation. It was shown that a neuroprotective role was gradually established against stroke, spinal cord injury and Parkinson’s disease. The aim of this study was to explore the role of the AMPK pathway in neuronal apoptosis in the hippocampus using a rat model of PTSD. The model PTSD rats received acute exposure to prolonged stress (single prolonged stress, SPS), followed by examination of the effects of genes and/or proteins related to the AMPK and oxidative stress pathways in the hippocampus with or without metformin preconditioning. The results indicated that the level of phosphorylated AMPK was markedly increased after SPS. Metformin protected the hippocampus as evidenced by abolishing down-regulation of the AMPK pathway and up-regulating expression of oxidative stress-related genes. These results indicated that metformin attenuated oxidative stress in the hippocampus in rats under SPS. AMPK pathway activation may be a novel therapeutic protocol for PTSD patients.
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Acknowledgements
The authors are grateful to all of the staff members of the China Medical University Experiment Center for their technical support. This study was funded by the National Natural Science Foundation of China (No. 31140060), the Shenyang Science and Technology Project (No. F16-205-1-35) and the Specialized Research Fund for Doctoral Program of Higher Education (No. 20132104110021). We thank the LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.
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This study was carried out in strict accordance with the recommendations of the Guide for the Care and Use of the Laboratory Animals of the National Health and Medical Research Council of China. The experimental protocol was approved by the Department of Psychiatry, China Medical University Animal Ethics Committee, and was endorsed by the Research and Ethics Committee of the Liaoning Key Lab of Biological Psychiatry, China.
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Wang, J., Xiao, B., Han, F. et al. Metformin Alleviated the Neuronal Oxidative Stress in Hippocampus of Rats under Single Prolonged Stress. J Mol Neurosci 63, 28–35 (2017). https://doi.org/10.1007/s12031-017-0953-6
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DOI: https://doi.org/10.1007/s12031-017-0953-6