Influence and implication of high-altitude hypoxia exposure on autophagy of hippocampal neurons

MA Wenke; LUO Peng; DAI Shuhui; YANG Yuefan; RAO Wei; PENG Cheng; WANG Jiu; FEI Zhou

Abstract：Objective This study aims to investigate the influence of high-altitude (6000 m) hypoxia exposure for different duration on negative emotions and hippocampal neuronal injury and autophagy of mouse and their interrelation.Methods Hypobaric oxygen chamber was used to simulate 6000 m altitude circumstances.Treatment groups were exposed to high-altitude hypoxia circumstances for different time,and control group was raised outside the hypobaric oxygen chamber.Elevated plus maze (EMP) test was used to investigate the negative emotions after high-altitude hypoxia exposure.The pathological morphology of hippocampal neurons in CA1 area was examined by HE staining.Expressions of hypoxia-inducible factor 1α (HIF-1α),Bcelin-1 and microtubule-associated protein 1 light 3-Ⅱ (LC3-Ⅱ) was assayed by Western Blot.Results Significant reductions after high altitude hypoxia exposure for 1,3,and 14 d in the percentage of residence time and the entries in the open arms indicated by EMP test was observed.HE staining showed that the hippocampal neurons in CA1 area after high-altitude hypoxia exposure for 1,3,and 14 d were arranged disorderly,with dilatate intercellular spaces and irregular shape and karyopyknosis.And compared with other treatment groups,injury of hippocampal neurons after 7 d high-altitude hypoxia exposure was attenuated relatively.The expressions of HIF-1α,Beclin-1 and LC3-Ⅱ peaked after high altitude hypoxia exposure for 1 d and then decreased.At treatment for 7 d,there were no significant difference in the expressions of HIF-1α and LC3-Ⅱ compared with the control group.Conclusion At high-altitude hypoxia circumstances,increased negative emotions of mouse were related with the damage of hippocampal neurons,and the activation of autophagy may be involved in the damage of hippocampal neurons.