The effect of severe intermittent hypoxia on cognitive function and expression of phosphorylated p38MAPK in rat hippocampus CA1 / 中华行为医学与脑科学杂志

ABSTRACT

Objective To explore the mechanism of severe intermittent hypoxia on oognitive function by evaluatig the effect of chronic intermittent hypoxia on cognitive function,neurons structure,damage,p38MAPK protein expression and neuronal apoptosis in rats hippocampal CA1.Methods Ninety-six mature and male Wistar rats were randomly divided into two groupscontrol group (UC) and 5％ chronic intermittent hypoxia group (5％CIH).Rats in IH groups were suffered 8 hours intermittent hypoxia everyday,and the duration of experiment was respectively 2,4,6 and 8 weeks.After exposed for 2,4,6,and 8 weeks,the cognitive function of rats was assessed with the Morris water maze (MWM) ; the changes in the morphology of nerve cells in hippocampus CA1 region were observed; the expression of phosphorylated p38MAPK protein in hippocampus was detected by the methods of immunohistochemistry and western blot; the apoptosis of nerve cells was detected by the method of TUNEL.Results Compared with control group,with prolonged hypoxia,the time of escape latency obviously prolonged and the time of across the target quadrant shortened significantly in rats of 5％ CIH group.The time of escape latency at the 8th week was the longest ((71.71 ± 5.49)s,P＜ 0.05) in 5％ CIH group,and the time of across the target quadrant at the 8th week was the shortest ((26.82 ± 4.30) s,P ＜ 0.05) in 5％ CIH group.There appeared neuronal degeneration and necrosis in hippocampus CA1 in 5％ CIH group.Compared with the control group,the density of the nerve cells survival in the region of hippocampal CA1 reduced dramatically at the 2nd,4th,6th and 8th week and was the lowest at the 8th week(14.16 ± 2.07,P ＜ 0.05).By Immunohistochemical method,the expression of phosphorylated p38 MAPK of 5％ CIH group in hippocampal CA1 was more than UC group at the 2nd,4th,6th and 8th week.By western blot,the expression of phosphorylated p38MAPK of 5％ CIH group was more than UC group at the 2nd,4th,6th and 8th week and was the most at the 6th week (2.45 ± 0.14,P＜ 0.05) ;the index of neuronal apoptosis in hippocampal CA1 was increased significantly at the 2nd,4th,6th and 8th week than UC group and reached to the peak at the 6th week (0.608 ± 0.069,P ＜ 0.05) in the 5 ％ CIH group.Conclusion Chronic intermittent hypoxia could cause the activation of p38MAPK/pathway of neuronal apoptosis and was important mechanism of cognitive dysfunction at the early and middle stage.