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Intermittent hypoxic preconditioning relieves fear and anxiety behavior in post-traumatic stress model mice

DING Fu-Sheng^1,2, CHENG Xiang², ZHAO Tong², ZHAO Yong-Qi², ZHANG Guang-Bo², WU Hai-Tao², ZHU Ling-Ling^2,*, WU Kui-Wu²

¹Graduate School of Anhui Medical University, Hefei 230023, China；²Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Beijing 100850, China

Abstract

Intermittent hypoxia (IH) has preventive and therapeutic effects on hypertension, myocardial infarction, cerebral ischemia and depression, but its effect on post-traumatic stress disorder (PTSD) has not been known. In this study, we used inescapable electric foot shock combined with context recapture to build PTSD mouse model. The levels of fear and anxiety were valued by the open field, the elevated plus maze (EPM) and the fear conditioning tests; the level of spatial memory was valued by Y maze test; the number of Fos positive neurons in hippocampus, amygdala and medial prefrontal cortex was valued by immunohistochemical staining; and the protein expressions of hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and brain derived neurotrophic factor (BDNF) in these brain area were valued by Western blot. The results showed that IH and model (foot shock) had an interaction on percentage of entering open arms (OE%) in EPM and freezing time and the number of fecal pellets in fear conditioning test. IH increased OE% in EPM and reduced the freezing time and the number of fecal pellets in fear conditioning test in PTSD model mice. At the same time, IH reduced the number of Fos positive neurons in the hippocampus, amygdala and medial prefrontal cortex of PTSD model mice, and increased the protein expression levels of HIF-1α, VEGF and BDNF in these brain tissues. In conclusion, IH pretreatment can relieve fear and anxiety behavior in post-traumatic stress model mice, suggesting that IH may be an effective means of preventing PTSD.

Key words: post-traumatic stress disorder; intermittent hypoxic preconditioning; Fos positive neurons; HIF-1α; BDNF

Received: 2019-01-11　　Accepted: 2019-03-14

Corresponding author: 朱玲玲　　E-mail: linglingzhuamms@126.com

DOI: 10.13294/j.aps.2019.0033

Citing This Article：

DING Fu-Sheng, CHENG Xiang, ZHAO Tong, ZHAO Yong-Qi, ZHANG Guang-Bo, WU Hai-Tao, ZHU Ling-Ling, WU Kui-Wu. Intermittent hypoxic preconditioning relieves fear and anxiety behavior in post-traumatic stress model mice. Acta Physiol Sin 2019; 71 (4): 537-546 (in Chinese with English abstract).