The Effects Of Intermittent Hypoxia On The Cognitive And The P38MAPK/Neurocyte Apoptosis In Rats

Objective:1Discussion on the effects of intermittent hypoxia on the cognitive function and hippocampus ultra microstructure in Rats;2to observe the effects on the p38MAPK/the neurocyte apoptosis in rats exposed to different degree of intermittent hypoxia. Method:256mature male Wistar rats were randomly assigned to4groups:Control group (UC),10%continued hypoxia group (10%CH),5%intermittent hypoxia group (5%CIH) and10%of chronic intermittent hypoxia Group (10%CIH), and rats in each4groups were assigned to2nd,4th,6th and8th week subgroups (n=16). Rats in each group were suffered8hours everyday. Intermittent hypoxia circulating to give different flow of nitrogen and compressed air (each cycle120s,at the first30s’keeping oxygen concentration inside at5%and10%for CIH groups, and at following40s’increasing oxygen concentration to21%; and keeping50s’). The same concentration of nitrogen and compressed air was given to the10%CH group to keep the oxygen concentration in room to21%for8hours. The compressed air was given to the UC group. The cognitive functions of rats in each group were assessed with the Morris water maze (MWM) at the end of experiments and hippocampus ultra microstructure was observed. The expression of phosphorylase p38MAPK protein was detected by immunohistochemical and western blot. The apoptosis of hippocampus cell was detected by TUNEL.Results:1. Morris water maze experimental results:Compared with UC group, in10%CH and10%CIH groups animals showed escape latency obvious extended and the time of through original platform location significantly reduced, especially at6th week. There was different in time that change starting, in5%CIH group, it was occurred at the2nd week, while in the10%CIH and10%CH group, at4th week.2. The results of morphology.①Mirror microscope:In3hypoxia groups, with the extension of exposure time, the number of hippocampus neurons and synaptic were decreased, the structure injury was significantly in nerve cell nucleus at all duration of experiment4th,6th and8th weeks in10%CH, while in two CIH groups, it occurred at the2nd week, earlier than in10%CH group.②SEM:In3hypoxia groups at early stage, morphological changes of hippocampal neurons are not obvious. With time being, showing increased never system damage in neurons cytoplasm, nuclear membrane, rough endoplasmic, mitochondria, axonal flow, axonal neurofilament otmesis, and so on, especially in5%CIH group.3. Phosphorylation p38MAPK immunohistochemical results:compared with the UC group, in three hypoxia groups at2nd,4th,6th,8th week, phosphorylation p38MAPK-positive cells in hippocampus increased markedly, to the peak at6th week; Comparing with10%CH, two CIH groups in the2nd,4th,6th,8th,phosphorylation p38MAPK-positive cells in hippocampus increased significantly, especially in5%CIH. group.4. Phosphorylation p38MAPK Western blot results:compared with the UC group,10%CH and10%CIH5%CIH group in2nd,4th,6th,8th week, phosphorylation p38MAPK expression in hippocampus increased markedly, reaching to the peak in the6th week; Compared with the10%CH group,10%CIH,5%CIH group in2nd,4th,6th,8th week, phosphorylation p38MAPK-positive cells in hippocampus increased significantly, especially in5%CIH. group.5. TUNEL test results:compared with UC, in three hypoxia groups, at2nd,4th,6th,8th week neuron apoptosis was significantly increased in hippocampus, at the6th week to the peak; Compared with the10%CH group,10%CIH,5%CIH group in2nd,4th,6th,8th week, neuron apoptosis increased significantly, especially in5%CIH.group. Conclusion:1. CIH can cause cognitive impairment in rats, it was related with severity and the duration of hypoxia, it occurs at early stage in severe CIH.2Hippoeampal injuries in the presence of different degrees of CIH was one of the mechanisms of learning and memory impairment in rats;3.It can activate the p38MAPK pathway in Rats exposure under the varying degrees of CIH and p38MAPK pathway is one of the important factors leading to apoptosis;4. CIH can cause varying degrees of p38MAPK/neurons apoptosis pathway activation; it is the important reasons of learning and memory impairment in rats after intermittent hypoxia. The cognitive and nerve system damage caused by CIH is severe than CH, especially at early stage.