Effects Of Voluntary Wheel Running On The Intracranial Inflammation,Cognition And Emotion Responses In Mice Induced By A?_1-42

Objective:To observe the effects of the voluntary wheel running on the spatial memory abilities,the emotion and the expression of the NF-?B,TNF-? and IL-10 in the amygdala and the hypothalamus of the Alzheimer's disease(AD)mice,to explore the possible mechanism of improving spatial memory ability and emotion in voluntary wheel running,and to provide new ideas for treatment of AD.Methods:The model of AD was prepared by intracerebroventricular injection of A?1-42 oligomer,and the control group was treated with the same method,equal volume of DMSO solvent was injected into the intracerebroventricular.After making the AD model for a week,to test that whether the model was successful,the Y-maze experiment was used.If the model was proved to be succeed,then the AD mice would be randomly divided into no-exercise group and exercise group.The mice among exercise group was trained by voluntary wheel running for 6 weeks,and at the same time,the mice of no-exercise group and the DMSO group had no training.After the training,the spatial memory ability of the three groups mice was tested by the Ymaze experiment,and the anxiety and depression were respectively assessed by the elevated plus-maze and the forced swimming.Then the statistical data was analyzed.Thereafter,the proteic expression of the NF-?B,TNF-? and IL-10 in the amygdala and hypothalamus of the three groups were detected by Western Blot and immunofluorescence staining.Results:1.After making the AD model for a week,AD group mice spent less time in new arm than DMSO group(P < 0.01));after the voluntary wheel running,the time of the exercise group in new arm was as 1.7 times as the AD group,meanwhile the exercise group had no difference with the DMSO group(P < 0.01).2.The percentage of time spent in open arms of the exercise group was significantly higher than that of AD group(P < 0.01),meanwhile exercise group had no difference with DMSO group in elevated plus-maze experiment.3.The results of the forced swimming test showed that the immobility time in exercise group was obviously lower than that of AD group(P < 0.001).4.In the amygdala brain region,immunofluorescence staining showed that in the AD group,the positive expression rate of pro-inflammatory cytokine NF-?B and TNF-? was obviously higher than that of the AD exercise group and the DMSO control group(P < 0.05),but the positive rate of anti-inflammatory cytokine IL-10 was significantly lower than that of the other two groups(P < 0.05).There was no significant difference between AD exercise group and DMSO group(P > 0.05).The results of Western blotting were consistent with those of immunofluorescence staining(P < 0.05).5.The results of immunofluorescence staining and Western blotting in the hypothalamus area were consistent with those in the amygdala.The proteic expression of NF-?B and TNF-? in the AD group were higher than that of the AD exercise group and the DMSO group(P < 0.05),but the expression of IL-10 in AD group was lower than that of the other two groups(P < 0.05).Conclusion:1.The voluntary wheel running can not only effectively enhance the spatial memory,but can also relieve the emotion of anxious and depression of the AD model mice.2.The voluntary wheel running can inhibit the release of TNF-?,NF-?B and upregulated the expression of anti-inflammatory cytokine IL-10 in the amygdala and the hypothalamus.3.The improvement of cognitive and emotional disorders in AD model mice may be through the regulation of inflammatory response.