| Objective: To monitor the spatial learning and memory ability changes of obstructive sleep apnea syndrome(OSAS)rats.To detect the changes of DDHD2 and ERC2 protein expression in hippocampus of experimental rats,and to observe the ultrastructural changes of presynaptic active zone.Methods: 22 male Sprague Dawley(SD)rats were randomly assigned into normal control group and OSAS model group,with 11 rats each group.Rats experimental model was established by simulating the OSAS process with chronic intermittent hypoxia(CIH)environment.The spatial learning and memory ability changes of experimental rats were observed with Morris water maze(MWM).DDHD2 and ERC2 protein expression in hippocampus of experimental rats was observed using Western Blot.And the expression location of DDHD2 and ERC2 in hippocampal CA1 region neurons was observed by immunohistochemistry.Finally,the ultrastructural changes of presynaptic active zone were observed under a Transmission Electron Microscope.Results: Establishment and evaluation of OSAS model: Compared with normoxic environment,OSAS rats in hypoxic environment showed hypoxia manifestations,including less activity,increased sleep,accelerated respiratory rate and lift-head breath.Meanwhile,the monitored caudal artery blood oxygen saturation(Sp O2)of rats in hypoxic environment fluctuated between 69% and 82%,and the Sp O2 fluctuated between 96% and100% in normoxic environment.MWM results: The escape latency of the two groups of experimental rats in place navigation test continuously got shorter with the increase of repetitive training every day.For normal control group,it was(39.4 ± 11.0 on the first day,32.4 ± 7.9 on the second day,17.4±5.9 on the third day,11.4±4.8 on the four day,8.0±3.1on the fifth day).While for OSAS model group,it was(46.8 ± 12.4 on the first day,43.6 ±10.7 on the second day,32.3±9.5 on the third days,26.6±8.1 on the four day,22.1±7.1 on the fifth day).The escape latency of OSAS model group for different days was longer than that of normal control group and the difference between the two groups was statistically significant(P<0.05).Spatial probe test: The original target platform passing-through number of experimental rats was(normal control group 5.3 ± 2.1,OSAS model group 3.1± 1.7),suggesting that the number of model group rats was less than that of normal control group,with statistical significance(P<0.05).The time percentage in target quadrant was(normal control group 31.5 ± 5.6,OSAS model group 24.2 ± 7.1),suggesting that the time percentage of model group rats was lower than that of normal control group,with statistical significance(P<0.05).Western Blot results: The gray value of DDHD2 protein expression in hippocampus of OSAS model rats was higher than that of normal group(normal group 1.03 ± 0.39,OSAS model group 1.47 ± 0.37,P<0.05).The gray value of ERC2 protein expression of model group was lower than that of normal control group(normal control group 0.50 ± 0.20,OSAS model group 0.29 ± 0.14,P<0.05).The difference was statistically significant.It was observed by immunohistochemistry that DDHD2 was expressed in the cytoplasm and nucleus of experimental rats hippocampal CA1 region neurons.ERC2 was expressed in the cytoplasm of experimental rats hippocampal CA1 region neurons.Transmission electron microscopy results: The presynaptic active zone length of model group rats hippocampal CA1 region reduced(normal group 0.30 ± 0.05,OSAS model group 0.21 ± 0.06),which was significantly different from that of normal group(P<0.01).Conclusion: On the experimental animal model established by CIH simulating OSAS,presynaptic ultrastructural changes and cognitive disorders,including learning-memory ability deficiency,which might be related to the associated DDHD2 overexpression and ERC2 down-regulated expression. |
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