Effect Of Chronic Intermittent Hypoxia On The Level Of Autophagy In Mice Hippocampal CA1 Neurons

Objective To explore the effect of chronic intermittent hypoxia (CIH) on the level of autophagy in mice hippocampal CA1 neurons.Method We establish the chronic intermittent hypoxia mice Model with gas control system and hypoxic chambers, in which the nitrogen and compressed air were circulated at 60 seconds per cycle. Male ICR mice (n=60) were used for experiments, which were randomly assigned to two groups: normoxic control (UC) and CIH (CIH). Each group were subdivided into four subgroups: the day 3 group (group A), Week 1 (group B), Weeks 2 (group C), Weeks 3 (group D) and weeks 4 (group E). The changes of morphological characteristics including autophagic vacuole in mice hippocampal CA1 neurons were observed by transmission electron microscope(TEM); and the method of Western-blot was used to detect the levels of LC3-II/LC3-Ⅰin the mice hippocampal CA1 neurons.Result (1) TEM results showed that as early as 3rd days after initiation of CIH, morphological changes including increased numbers of autophagy bodies,lysosomes and a dictyosome containing a complete, typical autophagosome with double membrane structure were observed in the chronic intermittent hypoxia mice hippocampal CA1 neurons.(2) Compared with those in the control group , the radio of LC3-II/LC3-I in happocampal CA1 neurons of mice exposed to CIH were significantly elevated, and with time exposed to CIH extended, it was followed by gradually progressive increase. And of which ,the increases of LC3-II/LC3-I in mice exposed to CIH for 3d,1w and 2w were slight , and radio of LC3-I/LC3-II in mice exposed to CIH for 3w and 4w reached higher point, which elevated by about 60% and 84%, respectively(P<0.01). Conclusion Chronic intermittent hypoxia (CIH) can induce the activation of autophagy in mice hippocampal CA1 neurons , Such mechanisms may underlie the neural function damage seen in obstructive sleep apnea syndrome.