| Objectives:In this paper,by studying the effects of high-intensity interval training intervention on learning and cognition of C57BL/6J wild-type mice and APP/PS1 transgenic mice and other morphological indexes and related protein indexes,the study and cognition function of mice in each program group and high-intensity interval The relevance of training,while screening the differentially expressed proteins related to learning and cognition in the hippocampus of the brain,and exploring the possible mechanism of action of high-intensity interval training intervention in relieving and preventing Alzheimer's disease.Method:C57BL/6J wild mice and APP/PS1 mice were fed with normal diet for 2 weeks.A total of 100APP/PS1 female 12-week-old mice(n=50)and ordinary C57BL/6J wild mice(n=50)were subjected to a week of adaptive training.According to the adaptation and training of each mouse to the treadmill,20 APP/PS1 mice and 20 ordinary C57 wild mice were eliminated(because APP/PS1 mice record their numbers by amputated toes,the mice with middle toes can not move normally,Therefore weed out),divide the remaining 60 mice into four groups,15 mice in each group,for one week of adaptive training(13 weeks of age).Grouping situation: normal quiet control group(C group,n=15),MCI quiet control group(M group,n=15),high-intensity intermittent exercise group(CT group,n=15),MCI high-intensity intermittent exercise group(MT group,n=15).There was no significant difference in body weight between the groups.The high-intensity interval exercise program is: the CT group and the MT group mice first undergo a one-week treadmill adaptation training(warm-up,10m/min×10 min;every 2 minutes,5 groups of high-intensity training are performed at a speed of 10m/min.Min increased to 20m/min),and then a 6-week formal training(10min warm-up,10m/min;1 group of high-intensity training every 2min,a total of 10 groups of training,each group lasts 5min;exercise 5 days a week).The maximum exercise capacity of each mouse is tested every other week to adjust the running speed to the maximum speed that they can maintain 10 intervals.Exercise ability test: 15 min warm-up,speed is 9.6m/min,running speed increases by 1.8m/min every 2min,test the maximum running speed that mice can reach.After HIIT intervention,Morris water maze experiment(including space exploration experiment and positioning navigation experiment)was used to test the learning and memory ability of animals.After the behavioral test,the animals were subjected to HIIT for 1 week to maintain the effect of exercise intervention.They were anesthetized with 10% water and chloral solution and then sacrificed.The brain was decapitated and the hippocampus tissue was removed and stored in liquid nitrogen.Then the sample was moved to-80? Ultra-low temperature to be tested.Western blot was used to detect A?42,phosphorylated Tau,HIF-1?,NGB,GLUT1,GLUT3,and cytochrome C protein in hippocampus.Results:(1)Differences in behavior between groups: Through 4-day positioning navigation and 1-day space exploration experiments,it was found that HIIT improved the cognitive function of C57BL/6J and APP/PS1 mice.On day 1 and day 2,there was no significant difference in latency time between the 4 groups of mice.On the 3rd day,the incubation period of mice in the M group was almost unchanged compared to the first day,while the incubation period of mice in the other groups was significantly reduced compared to the first day.At the same time,from the data on day 3,the incubation period of mice in group M showed no significant difference with the increase in days,and the incubation period on day 4 was significantly higher than that in group C(P<0.05),and it was significantly higher on day 4 MT group(P<0.05).In the space exploration experiment on the fifth day: the staying time of the MT group mice in the platform quadrant was significantly longer than that of the M group mice(P<0.05).(2)Differences in protein expression between groups:(1)Comparison between the normal group and the cognitive impairment group,namely C57BL/6J quiet group(C group)and APP/PS1 quiet group(M group): compared with C group,A? amyloid in group M was significantly increased(P<0.01);phosphorylated Tau protein was significantly increased(P<0.05);NGB level was significantly decreased(P<0.01);GLUT1 level was significantly decreased(P<0.05);GLUT3 level Significantly reduced(P<0.05);Cytochrome c level was significantly increased(P<0.0);(2)The comparison between the normal quiet group and the normal exercise group,namely the C57BL/6J quiet group(C group)and the C57BL/6J exercise group(CT group): Compared with group C,HIF-1? in CT group was significantly increased(P<0.01);NGB level was significantly increased(P<0.01);GLUT1 level was significantly increased;GLUT3 level was significantly increased(P<0.01)).(3)Comparison between the cognitively impaired quiet group and the cognitively impaired exercise group,namely APP/PS1 quiet group(M group)and APP/PS1 exercise group(MT group): Compared with M group,A? amyloid in MT group Significantly reduced(P<0.05);phosphorylated Tau protein was significantly reduced(P<0.05);HIF-1? level was significantly increased(P<0.01);NGB level was significantly increased(P<0.05);GLUT1 level was significantly increased(P<0.05);GLUT3 level increased significantly(P<0.05);Cytochrome c decreased significantly(P<0.05).(4)Compared between the normal exercise group and the cognitively impaired exercise group,that is,the C57BL/6J exercise group(CT group)compared with the APP/PS1 exercise group(MT group),the CT group NGB level was significantly higher(P<0.01);GLUT3 The level was significantly increased(P<0.01).Conclusions:This study found that exercise activated HIF-1? to regulate glucose transport and the neuroprotective effect of NGB to reduce the levels of A? and phosphorylated Tau in the brain,so as to improve the oxidative stress,neuroinflammation and excessive cell apoptosis in the brain of mice,thereby increasing The cognitive function of mice achieves the purpose of preventing and relieving Alzheimer's disease. |
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