Objective:To observe the effects of exercise training on the memory ability of rats with vascular cognitive im-pairment(VCI)and to explore the possible mechanisms of action.Method:Rat models of VCI were constructed by permanently ligating bilateral common carotid arteries,and were randomly divided into sham-operated groups(Sham,n=8),exercise-training groups(VCI+Ex,n=8),and control groups(VCI,n=8)according to the randomized numerical table method.The exercise training group started moderate-intensity aerobic exercise training on a small animal treadmill at 48 hours postoperatively,and the intensity of the exercise was increased day by day(5m/min—11m/min)in the first week,and was per-formed at a constant speed of 11m/min for 30 min per day,5 days per week in the second to fourth weeks.Rats in the sham-operated group and the control group were placed in the small animal treadmill at the same time points,but not turned on,for 30 min per day,5 days per week for 4 weeks.For the rest of the time,rats in each group were put back into the rearing cages and were free to eat,drink and move around.After completing the above experiments,the memory ability of rats in each group was evaluated by Novel Object Recognition(NOR)and Y-maze experiments;then the rats were euthanized by overdose anesthesia,and the hip-pocampal tissues were isolated and extracted from the brain.The distribution of N-methyl-d-aspartate receptor(NMDAR)and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor(AMPAR)in the hippocampal re-gion was observed by immunofluorescence staining,and the expression levels of PlexinA4 and neuropilin-2 in the hippocampal region were detected by Western Blot.Result:In the Y-maze experiment,rats in the VCI+Ex group explored the novel arm more frequently than the VCI group,as well as explored for a longer period of time than the VCI group,with significant differences(P<0.05,P<0.001);in the NOR experiment,the cognitive index of novelty of rats in the VCI+Ex group was significantly higher than that of rats in the VCI group,and the difference was significant(P<0.001).Immunoflu-orescence results showed that compared with the VCI group,the expression levels of NMDAR,PlexinA4,and neuropilin-2 in the hippocampal region of the VCI+Ex group were significantly higher(P<0.01,P<0.05,P<0.05,respectively),while there was a tendency for the expression of AMPAR and the ratio of NMDAR/AM-PAR to be elevated.Western Blot results showed that PlexinA4 expression in the hippocampus of VCI+Ex rats was higher than that of the VCI group,and the results were significantly different(P<0.05).Conclusion:Exercise training can improve the memory ability of VCI rats,and the possible mechanism is to promote the expression of NMDAR,PlexinA4 and neuropilin-2 in the hippocampus,which in turn enhances the synaptic plasticity in the hippocampus.

Objective:To explore the effect of exercise on the memory of rats modeling vascular cognitive impairment (VCI) and also its effects on the hippocampal Sema3G/neuropilin-2 (Nrp2)/PlexinA4 signaling pathway.Methods:Eighteen male Sprague-Dawley rats were randomly divided into a sham-operated group, a model group, and an exercise group, each of 6. The model and exercise groups underwent VCI modeling via bilateral common carotid artery occlusion, while the sham-operated group received the same surgical procedure without vessel ligation or transection. Beginning forty-eight hours after the surgery, the exercise group carried out daily 30-minute treadmill training sessions, 5 days a week, for a total of 4 weeks, while the other two groups were placed on the same treadmill with it not in operation. After the intervention, cognitive functioning was assessed using the novel object recognition (NOR) test and a Y-maze test. Western blotting was employed to evaluate the expression of Sema3G, Nrp2, PlexinA4, and Rac1 in the hippocampus. Immunofluorescence staining was used to observe the distribution of Nrp2 and PlexinA4 in the hippocampus.Results:Compared with the model group, the exercise group exhibited significantly higher NOR indices during both the short-term and long-term memory testing phases after the intervention. Those rats also tended to have significantly longer total exploration times in the novel arm of the Y-maze test. The western blotting revealed that the expression levels of Sema3G, PlexinA4, and Rac1 in the hippocampus were significantly higher in the exercise group compared to the model group, on average. Immunofluorescence showed significantly increased PlexinA4 fluorescence intensity in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus, and significantly elevated Nrp2 fluorescence intensity in the CA3 region in the exercise group compared to the model group. The Pearson correlation coefficients for Nrp2/PlexinA4 co-localization in the CA1, CA3 and DG regions were significantly higher in the exercise group than in the model group.Conclusions:Exercise training significantly improves memory function in rats with VCI, and this effect may be associated with activation of the hippocampal Sema3G/Nrp2/PlexinA4 signaling pathway.

Objective:To observe the effects of exercise training on the memory ability of rats with vascular cognitive im-pairment(VCI)and to explore the possible mechanisms of action.Method:Rat models of VCI were constructed by permanently ligating bilateral common carotid arteries,and were randomly divided into sham-operated groups(Sham,n=8),exercise-training groups(VCI+Ex,n=8),and control groups(VCI,n=8)according to the randomized numerical table method.The exercise training group started moderate-intensity aerobic exercise training on a small animal treadmill at 48 hours postoperatively,and the intensity of the exercise was increased day by day(5m/min—11m/min)in the first week,and was per-formed at a constant speed of 11m/min for 30 min per day,5 days per week in the second to fourth weeks.Rats in the sham-operated group and the control group were placed in the small animal treadmill at the same time points,but not turned on,for 30 min per day,5 days per week for 4 weeks.For the rest of the time,rats in each group were put back into the rearing cages and were free to eat,drink and move around.After completing the above experiments,the memory ability of rats in each group was evaluated by Novel Object Recognition(NOR)and Y-maze experiments;then the rats were euthanized by overdose anesthesia,and the hip-pocampal tissues were isolated and extracted from the brain.The distribution of N-methyl-d-aspartate receptor(NMDAR)and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor(AMPAR)in the hippocampal re-gion was observed by immunofluorescence staining,and the expression levels of PlexinA4 and neuropilin-2 in the hippocampal region were detected by Western Blot.Result:In the Y-maze experiment,rats in the VCI+Ex group explored the novel arm more frequently than the VCI group,as well as explored for a longer period of time than the VCI group,with significant differences(P<0.05,P<0.001);in the NOR experiment,the cognitive index of novelty of rats in the VCI+Ex group was significantly higher than that of rats in the VCI group,and the difference was significant(P<0.001).Immunoflu-orescence results showed that compared with the VCI group,the expression levels of NMDAR,PlexinA4,and neuropilin-2 in the hippocampal region of the VCI+Ex group were significantly higher(P<0.01,P<0.05,P<0.05,respectively),while there was a tendency for the expression of AMPAR and the ratio of NMDAR/AM-PAR to be elevated.Western Blot results showed that PlexinA4 expression in the hippocampus of VCI+Ex rats was higher than that of the VCI group,and the results were significantly different(P<0.05).Conclusion:Exercise training can improve the memory ability of VCI rats,and the possible mechanism is to promote the expression of NMDAR,PlexinA4 and neuropilin-2 in the hippocampus,which in turn enhances the synaptic plasticity in the hippocampus.

Objective:To explore the effect of exercise on the memory of rats modeling vascular cognitive impairment (VCI) and also its effects on the hippocampal Sema3G/neuropilin-2 (Nrp2)/PlexinA4 signaling pathway.Methods:Eighteen male Sprague-Dawley rats were randomly divided into a sham-operated group, a model group, and an exercise group, each of 6. The model and exercise groups underwent VCI modeling via bilateral common carotid artery occlusion, while the sham-operated group received the same surgical procedure without vessel ligation or transection. Beginning forty-eight hours after the surgery, the exercise group carried out daily 30-minute treadmill training sessions, 5 days a week, for a total of 4 weeks, while the other two groups were placed on the same treadmill with it not in operation. After the intervention, cognitive functioning was assessed using the novel object recognition (NOR) test and a Y-maze test. Western blotting was employed to evaluate the expression of Sema3G, Nrp2, PlexinA4, and Rac1 in the hippocampus. Immunofluorescence staining was used to observe the distribution of Nrp2 and PlexinA4 in the hippocampus.Results:Compared with the model group, the exercise group exhibited significantly higher NOR indices during both the short-term and long-term memory testing phases after the intervention. Those rats also tended to have significantly longer total exploration times in the novel arm of the Y-maze test. The western blotting revealed that the expression levels of Sema3G, PlexinA4, and Rac1 in the hippocampus were significantly higher in the exercise group compared to the model group, on average. Immunofluorescence showed significantly increased PlexinA4 fluorescence intensity in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus, and significantly elevated Nrp2 fluorescence intensity in the CA3 region in the exercise group compared to the model group. The Pearson correlation coefficients for Nrp2/PlexinA4 co-localization in the CA1, CA3 and DG regions were significantly higher in the exercise group than in the model group.Conclusions:Exercise training significantly improves memory function in rats with VCI, and this effect may be associated with activation of the hippocampal Sema3G/Nrp2/PlexinA4 signaling pathway.