Effects Of Aerobic Exercise On Hippocampal NEK7/Caspase-1/IL-1β Expression And Learning And Memory Ability Of APP/PS1 Mice

Objective: To investigate the effects of aerobic exercise on the expression of β-amyloid1-42(Aβ1-42),NIMA-related kinase 7(NEK7),Cysteine aspartase-1(Caspase-1)and Interleukin-1β(IL-1β)in the hippocampus of Alzheimer’s disease(AD)model mice and their spatial learning and memory ability.Method:Selecting 3-month-old adult C57 male mice(n=12)as Wild-type Control group,and choosing APP/PS1 transgenic male mice randomly with the same age for AD Control group(n=12)and AD Runner group(n=12).Feeding adaptively for 1 week,starting a5-month platform running exercise with a speed of 12-15m/min.After platform running,using Morris water maze(MWM)and eight-arm radial maze(RM)test the spatial learning and memory ability of each group.Nissl’s staining,Quantitative real-time polymerase chain reaction(q PCR),Immunofluorescence(IF)and Western Blot(WB)were used to monitor the hippocampal neurons and the expression of Aβ1-42,NEK7,caspase-1 and IL-1β in the hippocampus of mice.Results:(1)Ethology: MWM : In the escape latency,AD Control was significantly longer than Wild-type from day 2(P <0.01 of each day);No significant difference existed between AD Runner and Wild-type(P > 0.05);AD Runner was significantly shorter than AD Control(P < 0.01 of each day).Number of crossing platforms: On day 7,AD Control significantly less than Wild-type(P<0.01),and AD Runner was higher significantly than AD Control(P<0.01).RM: The working memory errors: AD Control was higher than Wild-type significantly(P<0.01),and AD Runner was lower than AD Control arrestingly(P<0.05);The number of reference memory errors: AD Runner was lower than Wild-type(P>0.05),AD Control was higher than Wild-type prominently(P<0.01),it was also significantly higher than AD Runner(P<0.01);The rate of correct: AD Control was lower than Wild-type remarkably(P<0.01),while AD Runner was slightly higher than Wild-type(P>0.05),but higher than AD Control significantly(P<0.01).(2)Nissl’s staining:Wild-type Nissl bodies have the darkest staining,uniform coloration and the largest number,and the cell distribution is reasonable;AD Control have the lightest staining and fewer numbers,with unclear nucleoli,sparse cell arrangement,and large gaps.The staining depth,number and size of Nissl bodies in AD Runner was slightly better than those in AD Control,and the cell distribution is also slightly more compact.(3)IF in CA3 area:Aβ1-42 : AD Control and AD Runner was higher than Wild-type markedly(P<0.01,P<0.01),and AD Runner was significantly lower than AD Control(P<0.01);NEK7:AD Control and AD Runner was higher than Wild-type memorably(P<0.01,P<0.05),and AD Runner was significantly lower than AD Control(P<0.01).);Caspase-1: AD Control and AD Runner was significantly increased than Wild-type(P<0.01,P<0.05),and AD Runner was significantly lower than AD Control(P<0.01);IL-1β: AD Control and AD Runner were significantly higher than Wild-type(P<0.01,P<0.01),and AD Runner was significantly lower than Wild-type(P<0.01).(4)q PCR: Aβ1-42: AD Control and AD Runner were higher than Wild-type signally(P<0.01,P<0.01),AD Runner was significantly lower than AD Control(P <0.05);NEK7: AD Control was higher than Wild-type markedly(P<0.05),and there was almost no difference between AD Runner and Wild-type(P>0.05),but they were significantly lower than AD Control(P<0.05);Caspase-1: AD Control and AD Runner were significantly increased than Wild-type(P<0.01,P<0.05),and AD Runner was significantly lower than AD Control(P<0.01);IL-1β: AD Control and AD Runner were significantly higher than Wild-type(P<0.01,P<0.01),AD Runner was significantly lower than AD Control(P<0.05)).(5)WB: Aβ1-42: AD Control and AD Runner were significantly higher than Wild-type(P<0.01,P<0.01),AD Runner was significantly lower than AD Control(P<0.01);NEK7: AD Control and AD Runner were significantly higher than Wild-type(P<0.01,P<0.05),AD Runner was lower than AD Control significantly(P<0.05);Caspase-1: AD Control and AD Runner were higher than Wild-type observably(P<0.01,P<0.01),and AD Runner was significantly lower than AD Control(P<0.05);IL-1β: AD Control and AD Runner were significantly higher than Wild-type(P<0.01,P<0.01),and AD Runner was significantly lower than AD Control(P<0.01).Conclusion:(1)APP/PS1 mice have lessened spatial learning and memory ability,and aerobic exercise can improve that.(2)Aerobic exercise can alleviate the damage to the structure of neurons in the CA3 area of the hippocampus of APP/PS1 mice.(3)Aerobic exercise can down-regulate the expression of hippocampal Aβ1-42 in APP/PS1 mice,reduce the levels of NEK7,Caspase-1 and IL-1β in the hippocampus of APP/PS1 mice,suggesting that aerobic exercise may reduce NEK7 to decrease neuroinflammation,improves neuropathology in AD model mice,and delays cognitive decline.