The Effect Of Chronic Intermittent Hypoxia On Learning And Memory Ability In Rats

Objective:To create a chronic intermittent hypoxic animal model, as an experimental platform for further study of the pathogenesis of OSAHS. To study the effect of chronic intermittent hypoxia and removal of hypoxia on learning and memory ability in Sprague-Dawley rats , then to approach the possible mechanisms of learning and memory function in patients with OSAHS, and to provide a theoretical basis for the treatment of patients with OSAHS.Methods:Experiments were performed on 24 three-month-old male Sprague-Dawley rats, they were randomly assigned to three experimental groups (n=8/group): unhandled control group (UC), chronic intermittent hypoxia group (CIH), and Removal of hypoxia group (RH). Rats in UC group were raised normally, those in CIH group suffered 8H intermittent hypoxia everyday, the duration of experiment was 4 weeks, and those in RH group was the same as those in CIH group in previous 4 weeks and were raised normally in later 4 weeks. The learning and memory ability of rats in each group were assessed with the Morris water maze test at the end of the experiments. The expression of synaptophysin and GFAP in CA3 region of hippocampus was investigated by immunohistochemistry staining and image analysis, and observing the ultrastructural changes in the hippocampus of rats.Results:1. Morris water maze test learning scores (place navigation): the escape latency of rats in different days in UC group and RH group were significant difference (P<0.05), and that in first three days were no significant difference. (P> 0.05) From the beginning ,the escape latency of rats in CIH group was significantly longer than that in UC group and RH group (P<0.05), that in RH group was significantly longer than that in UC group (P<0.05).2. Morris water maze test memory scores: The number of times of crossing the platform in CIH group was significantly reduced than that in UC group (P<0.01), that in RH group was significantly reduced than that in UC group (P<0.05) and was significantly increased than that in CIH group (P<0.05); The percentage of time spent on crossing the target quadrant to the total swimming time in CIH group was significantly decreased compared with that in UC group (P<0.01), that in RH group was significantly decreased than that in UC group (P<0.05) and was significantly increased than that in CIH group (P<0.05).3. The expression of synaptophysin in CA3 region of hippocampus in CIH group and RH group was fewer than that in UC group (P<0.01), that in RH group was significantly more than that in CIH group (P<0.01).4. The expression of GFAP in CA3 region of hippocampus in CIH group and RH group was higher than that in UC group (P<0.01), that in RH group was significantly lower than that in CIH group (P<0.01).5. Observation in electron microscope that neurons of hippocampal CA3 of rats in CIH group array loose, electron density of the plasma increased, the number of synaptic density reduced and ultrastructural changed, and these changes in rats of RH group has clearly improved.Conclusion:1. Chronic intermittent hypoxia can make the function of learning and memory in rats drop, the function of learning and memory in the rats partly improve after removing the hypoxia factors.2. The decline of learning and memory ability may be related to chronic intermittent hypoxia, and its possible mechanism is that neurons and synapses of hippocampal CA3 region decrease and change function and structure by chronic intermittent hypoxia.