Voluntary Wheel Running Improve Learning And Memory Ability Of Alzheimer’s Disease Mice By Inhibiting NF-κB Pathway

Objective:To observe the effect of the learning and memory ability and the expression of inflammatory cytokines in the hippocampus of Alzheimer ’s disease after voluntary running wheel,investigate the mechanism of voluntary running to AD learning and memory ability and nerve inflammation,and to provide new ideas for the prevention and treatment of neurodegenerative diseases.Methods:45 male Kunming mice weighing 30 ~ 35 g were selected,Which were provided by Experimental Animal Center of Shanxi Medical University and were randomly divided into the following groups:(1)DMSO control group,(2)AD quiet group,(3)AD exercise group.The mice were anesthetized with an intraperitoneal injection of 3.5%chloral hydrate,the mice in DMSO control group was performed by intracerebroventricular injection of DMSO,the mice in AD exercise group and AD quiet group was performed by intracerebroventricular injection of Aβ1-42 oligomers by brain stereotaxic apparatus and according to the brain atlas.Seven day after i.c.v.Aβ1-42 or DMSO injection,the mice in AD exercise group were applied voluntary wheel running for 6 weeks,the mice in DMSO control group and AD quiet group were kept normal feeding and no exercise.At the end of 6 weeks of voluntary wheel running,the Morris water maze test was used to evaluate the effect of voluntary wheel running on learning and memory ability of all mice.The positive expression rate of TNF-α,IL-10,NF-κB in hippocampus of mice was by Immunofluorescence staining.The protein expression of inflammatory cytokines in hippocampus of mice was detected by Western blot.Results:Morris water maze test showed that after 6 weeks of exercise,the escape latency in the AD exercise group(12.10 ± 1.26)was significantly lower than that in the AD quiet group(27.75 ± 3.88)(P<0.01),suggested that the 6-week voluntary wheel running improved the learning and memory ability of the AD model.Immunofluorescence results showed that NF-κB,TNF-α and IL-10 were expressed in hippocampal CA1 and CA3 regions of DMSO control group,AD exercise group and AD quiet group,and the expression trend of each one were consistent.The positive expression rates of NF-κB and TNF-α in the AD quiet group were significantly higher than other two groups(P<0.05),the positive expression rate of IL-10 in AD quiet group was significantly lower than other two groups(P<0.05),but there was no significant difference between AD exercise group and DMSO control group(P>0.05).Western blot analysis showed that NF-κB and TNF-α had the highest protein expression in the AD quiet group,and the other two groups were significant difference(P<0.05),The expression of IL-10 in AD quiet group was the lowest,and it was higher in AD exercise group and DMSO control group,and the latter two are more close(P<0.05),and have statistically significant difference with the AD quiet group(P<0.05).Conclusions:(1)Voluntary wheel running can improve the learning and memory ability of AD model mice.(2)Voluntary wheel running down-regulated the release of proinflammatory cytokine TNF-α and up-regulated the expression of anti-inflammatory cytokine IL-10 in the hippocampus of AD model mice.(3)Inhibition of NF-κB pathway play a key role in voluntary wheel running improves the learning and memory ability of AD model mice.Voluntary wheel running can significantly inhibit over-activation of NF-κB,TNF-α cascade inflammation and regulate the hippocampus inflammatory response imbalance to improve the learning and memory ability of AD model mice.