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Objective To explore the effects of acteoside on dysfunction of learning and memory and the protective effect of oxidative stress in rats with vascular dementia.Methods 30 SD rats were randomly divided into sham group,model group,nicergoline group,low-dose acteoside group and high-dose acteoside group,with 6 rats in each group.Preparation of vascular dementia model by 2-vessed occlusion.The ability of exploring and learning and memory in rats were detected by step down test and avoid dark test.Determination of malondialdehyde (MDA),reactive oxygen species (ROS) and glutathione peroxidase (GSH-PX) activity in serum and brain tissue was conducted by Elisa.Results Autonomic activity test showed that the frequency and activity of autonomous activity in the model group were significantly lower than those in the sham group(P＜0.01),the frequency of autonomous activity in each administration group was significantly higher than that in the model group (P＜0.01),and the central activity time in the high-dose group was significantly higher than that in the model group (P＜0.01).Step down test and avoid dark test showed that the latency of the model group was significantly lower than that of the sham group.(Model group of step down test:(25.33 ± 3.01) s,Sham group of step down test:(56.83 ± 15.90)) (P＜ 0.01).(Model group of avoid dark test:(15.67 ± 3.61) s,Sham group of avoid dark test:(135.82±44.00) s) (P＜0.01).The latency of low dose group was significantly higher than that of model group.(Low dose group of step down test:(46.40±14.32) s) (P＜0.01).(Low dose group of avoid dark test (44.20± 8.26)s) (P＜0.05).Step down test and avoid dark test showed that the number of mistakes in the model group was significantly higher than that in the sham operation group(P＜0.01).The number of errors in nicergoline group and the low dose group was significantly lower than that in the model group (P＜0.01,P＜0.05).In serum,the content of MDA and ROS in model group was significantly higher than that in sham group (P＜0.01) while the activity of GSH-PX in model group was significantly lower than that of sham group.The content of MDA in the other groups was significantly lower than that in the model group (P＜0.01).The content of ROS in the nicergoline group and low dose group was significantly lower than that in the model group (P＜0.05,P＜0.0l).The activity of GSH-PX in high dose group was significantly higher than that in model group (P＜0.01).In brain tissue,the content of MDA and Ros in model group was significantly higher than that in sham group (P＜0.01).The content of MDA and ROS in low dose group and high dose group were significantly lower than that in model group (P＜0.05,P＜0.01).Conclusion Acteoside can improve the dysfunction of learning and memory and depressive mood disorder caused by vascular dementia and reduce oxidative stress injury by decreasing the content of MDA-ROS and increasing the activity of GSH-PX enzyme.
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Objective To explore the roles of glycogen synthase kinase-3β (GSK-3β) in cognitive dysfunction and emotional alterations after rat's chronic cerebral ischemia.Methods 51 SD rats were randomly divided into sham group (sham group,n=17),chronic cerebral ischemia group (2VO group,n=17),chronic cerebral ischemia group + LiCl group (2VO + LiCl group,n=17),according to the table of random number.All groups were intraperitoneally injected with LiCl or saline on 3rd,7th,14th,21 st and 28th day,and then produced the chronic cerebral ischemia models.On the 28th day after model,the spatial learning and memory,fear memory,and anxiety emotion were detected.Results The Morris water maze test showed that 2VO group spent longer latent time searching and finding the platform than sham group (4th day P＜0.01,3rd,5th,6th,7th day P＜0.05).2VO+LiCl group spent shorter latent time than 2VO group (4th day P＜0.01,5th,6th,7th day P＜0.05).After removing the platform,2VO group spent longer time arriving the former location than sham group (P＜0.05).And 2VO+LiCl group spent dramatically different time compared to 2VO group (P＜0.01).Step-down test showed 2VO group spent shorter latent time than sham group (2VO group:(41.00±1.87)s,sham group:(44.55±2.77)s) (P＜0.05).2VO+ LiCl group spent dramatically longer latent time compared to 2VO group (2VO +LiCl group:(43.40± 1.35)s) (P＜ 0.05).2VO group made much more mistakes times than sham group (P＜0.05).2VO+LiCl group made dramatically less mistakes times compared to 2VO group (P＜0.05).The elevated plus maze test showed 2VO group had much less ratio of retention time in open arms (among total arms retention time) than sham group (2VO group:(0.23± 0.01),sham group:(0.25± 0.01)) (P＜ 0.01).2VO + LiCl group had much larger ratio than 2VO group (2VO + LiCl group:(0.24±0.01),P＜0.05).2VO group had much less ratio of entry times in open arms (among total arms entry times) than sham group (P＜0.01).2VO+LiC1 group had much larger ratio than 2VO group(P＜0.05).Conclusion Chronic cerebral ischemia can lead to deterioration of learning and memory,and anxiety emotion for rats.However,inhibition of GSK-3β can ameliorate these alterations.
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Objective To explore the roles and related mechanisms of Protein Phosphatase 2A(PP2A) in cognitive dysfunction after the chronic cerebral ischemia.Methods 70 male Sprague Dawley rats in clean degree were divided into sham group,chronic cerebral ischemia group (Bilateral carotid arteries occlusion,2VO),and chronic cerebral ischemia group with PP2A activation group(2VO+aPP2A).The rats were injected intraperitoneally with 1.88 μmol/ml sodium selenate(15 μmol · kg-1 · d-1) or equal volume of saline for 4 weeks.After one month,the chronic cerebral ischemia models were reproduced by the occlusion of bilateral common caroid artery.Then the abilities of learning and memory were tested by Morris water maze,electrophysiological indices were recorded to analyze the LTP changes,and destribution of synaptic vesicles was observed by electron microscope.Results Morris water maze test showed that the 2VO group had significantly longer latent time than sham group in searching platform(P＜0.05),and the 2VO+aPP2A group had dramatically shorter latent time (P＜0.01) than that of 2VO group.Then removing platform to test the rats memory,the data showed that 2VO group spent markedly longer time than sham group to reach the location of the former platform (sham group:(14.50±1.98)s ; 2VO group:(17.30±2.11) s) (P＜0.01),and the 2VO+aPP2A group((15.09± 1.45) s) spent dramatically shorter latent time(P＜0.05) than that of 2VO group.The electrophysiological data showed that 2VO group had the noticeably smaller field excitable postsynaptic potential slope (fEPSP) slope ratio between pre and post of the high frequency stimulations (Long-term potential,LTP) than sham group(sham group:1.69±0.27; 2VO group:2.02±0.137) (P＜0.01),and the 2VO+aPP2A group(1.86±0.19) had strikingly higher ratio than that of 2VO group(P＜0.01).The electromicroscope observation showed that presynaptic vesicles density of 2VO was remarkably lower than that of sham group (sham group:(4.51±0.29) /μm2 ; 2VO group:(2.02±0.14) /μm2) (P＜0.01),and presynaptic vesicles density of 2VO+aPP2A group((3.58±0.50) /μm2) was noticeably higher than that of 2VO group(P＜0.01).Conclusion Activating PP2A can prevent the cognitive dysfunction after chronic cerebral ischemia through regulating LTP and synaptic vesicle density.And PP2A is probably a potential target for preventing and treating the cognitive dysfunction after chronic cerebral ischemia.