| Objective: By establishing APP/PS1 mice model of long-term aerobic exercise,determination the expression of A?1-42?NF-?B?NLRP3?IL-1??IL-10 in hippocampal after long-term aerobic exercise.To observe the effect of aerobic exercise on NF-?B/NLRP3 pathway on hippocampal neuroinflammation and learning and memory in APP / PS1 mice.Methods: Twelve 3-month-old adult C57 male mice were selected as wild control group(W),and 24 APP/PS1 transgenic mice of the same strain were randomly divided into AD control group(C)and AD exercise group(S),with 12 mice in each group.After one week of adaptive feeding,treadmill exercise was started at the speed of 12-15m/min for 5 months.After exercise,Morris Water Maze and 8-Arm Maze were used to test the spatial learning and memory ability of mice in each group.The expressions of A? 1-42,NF-?B,NLRP3,IL-1? and IL-10 in hippocampus of mice were detected by quantitative real-time PCR(q PCR),Immunofluorescence(If)and Western blotting(WB).Results: 1.Ethology:(1)Morris water maze positioning navigation: the results of Morris water maze escape latency experiment in the first 6 days showed that there were significant differences in the escape latency time of different group S: there was no difference in the time of each group on the first day(P>0.05),and the escape latency of each group gradually showed different differences from the second day,The escape latency of group C was longer than that of group W(P<0.05);There was no significant difference between the escape latency of group S and group W(P>0.05).On the 4th day,the escape latency of group S increased to a certain extent,and then continued to decrease;The escape latency of group W increased on the 5th day,which was significantly different from that of group C(P<0.01);There was no significant difference in escape latency between group W and group S(P>0.05).In the process of space exploration experiment,the number of mice crossing the platform in group W was significantly higher than that in group C(P<0.01);The number of crossing platform in group S was significantly higher than that in group C(P<0.05);There was no significant difference in the crossing times between group W and group S(P>0.05).(2)Eight arm maze: during the eight arm maze experiment,the number of working memory errors in group W was significantly lower than that in group C(P<0.05);The number of working memory errors in group C was significantly higher than that in group S(P<0.05);There was no significant difference in the number of working memory errors between group W and group S(P>0.05).The number of reference memory errors in group W was significantly lower than that in group C(P<0.01);The number of reference memory errors in group C was significantly higher than that in group S(P<0.01);There was significant difference in the number of reference memory errors between group W and group S(P<0.05).2.Results of molecular biology experiment:(1)Real-time PCR results: the m RNA expression of A? 1-42 in hippocampus of mice in group C and group S were significantly higher than that in group W(P<0.01,P<0.01);the m RNA expression of A? 1-42 in hippocampus of mice in group S was significantly different from that in group C(P<0.01).The m RNA expression of NF-?B in hippocampus of group C and group S were significantly higher than that of group W(P<0.01,P<0.01);the m RNA expression of NF-?B in hippocampus of group S was significantly different from that of group C(P<0.05).The m RNA expression of NLRP3 in hippocampus of group C and group S were significantly higher than that of group W(P<0.05,P<0.01);the m RNA expression of NLRP3 in hippocampus of group S was significantly higher than that of group C(P<0.05).(2)Western blotting results: the protein content of A? 1-42 in hippocampus of mice in group C and group S were significantly higher than that of mice in group W(P<0.05,P<0.05);the protein content of A? 1-42 in hippocampus of mice in group S and group C were significantly different(P<0.05);the protein content of NF-?B in hippocampus of group C was significantly higher than that of group W(P<0.01);the protein content of NF-?B in hippocampus of group S was significantly different from that of group C(P<0.05);the protein content of NF-?B in hippocampus of group S and group W was not significantly different(P>0.05).The m RNA expression of NLRP3 in hippocampus of group C and group S were significantly higher than that of group W(P<0.05,P<0.01);the m RNA expression of NLRP3 in hippocampus of group S was significantly higher than that of group C(P<0.05).The protein content of IL-1? in hippocampus of mice in group C and group S were significantly higher than that of mice in group W(P<0.01,P<0.05);the protein content of IL-1? in hippocampus of mice in group S and group C was significantly different(P<0.01).(3)Immunofluorescence detection results: the expression of related proteins in hippocampal CA1 region of mice in each group was as follows: A? 1-42:The mice in group C and group S were significantly higher than those in group W(P<0.01,P<0.01),and the mice in group C were significantly lower than those in group S(P<0.01);IL-1?:The mice in group C and group S were significantly higher than those in group W(P<0.01,P<0.05).The mice in group S was significantly higher than those in group C(P<0.05);IL-10:The mice in group C and group S were significantly higher than those in group W(P<0.01,P<0.05).The mice in group S was significantly higher than those in group C(P<0.01).Conclusion:(1)Aerobic exercise has intervention effect on APP/PS1 mice,and can improve the neuroinflammatory reaction in the hippocampus of APP/PS1 mice;(2)In the behavioral experiment,the learning and memory ability of ad exercise group was significantly higher than that of ad control group,indicating that aerobic exercise can improve the learning and memory ability of APP/PS1 mice by mediating NF-?B/NLRP3 pathway;(3)Aerobic exercise can improve the levels of NF-?B and IL-10 in the hippoca mpus of APP/PS1 mice,and reduce the levels of A? 1-42,NLRP3 and IL-1? in the hippocampus of APP/PS1 mice,and the expression of anti-inflammatory cytokine IL-10 in CA1 region was up-regulated,suggesting that aerobic exercise may affect the activity of NLRP3 inflammatory bodies by regulating NF-?B,which is one of the neurobiological reasons for the improvement of hippocampal neuroinflammation in APP/PS1 mice. |
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