Effects Of Different Loads Of Aerobic Exercise On The Expression Of Aβ1-42 And DCX In The Hippocampus And Learning And Memory Ability Of AD Mice

Objective: At present,there is no specific drug for the treatment of AD.Prevention and improvement of AD is an urgent task for public health.Long term regular exercise can reduce the risk of AD and delay the progress of AD.However,there are few reports about the appropriate load of different load aerobic exercise to improve AD.Therefore,different loads of aerobic exercise intervention were used to explore the effects of appropriate aerobic exercise load on amyloid β-protein(Aβ),the number of newborn neurons and learning and memory ability in hippocampus of AD mice.So as to provide suitable aerobic exercise load for anti AD.Methods: Twenty four 3-month-old C57 BL / 6J male SPF grade APP / PS1 double transgenic mice were randomly divided into 4 groups,n = 6 in each group: AD control group(ADC);AD low load exercise group(ADL);AD medium load exercise group(ADM);AD high load exercise group(ADH).Another group of wild type control group(WTC),n = 6.ADL group,ADM group and ADH group were given aerobic exercise intervention for 20 weeks according to the maximum running speed of 12 m / min,15 m / min and 18 m / min respectively.After 20 weeks,eight arm maze test and Morris water maze test were used to test the learning and memory ability of mice;Western blotting(WB)and immunofluorescence(IF)were used to detect the expression of Aβ1-42 and Doublecortin(DCX)in dentate gyrus(DG)of hippocampus.Results:(1)Morris water maze navigation experiment: On the first day,there was no significant difference in the time of mice searching for the platform hidden under the water surface(P>0.05).After learning for one day,the mice in each group.On the second day,the time of finding platform in ADC group was longer than that in WTC group(P<0.05),and it was significantly increased on the third to sixth day(P<0.01).However,there was no significant difference between the exercise groups and the WTC group(P>0.05).The results showed that ad caused severe learning and memory impairment in mice,and exercise could significantly improve it.On the3rd-6th day,the time of platform searching in ADM group was less than that in ADC group on the 4th day(P<0.05),and it was significantly reduced on the 3rd,5th and6 th day(P<0.01).Compared with ADL group,ADM group had less time to find platform on the 3rd day(P<0.05),and significantly less time on the 4th and 5th day(P<0.01).On the 3rd-6th day,the time of finding platform in ADH group was less than that in ADC group and ADL group on the 4th and 5th day(P<0.05),and it was significantly reduced on the 6th day(P<0.01).On the third day,ADH group was significantly higher than ADM group(P<0.05).(2)Morris water maze space exploration experiment: The number of crossing the original platform in ADC group was significantly less than that in WTC group(P <0.01),but there was no significant difference between the exercise groups and WTC group(P>0.05).The number of crossing the original platform in ADM and ADH group was significantly increased than that in ADC group(P<0.01),and the number of crossing the original platform in ADM and ADH group was also increased than that in ADL group(P<0.05).(3)8-Arm maze test: The number of working memory errors in ADC group was significantly higher than that in WTC group(P<0.01),and there was no significant difference in working memory and reference memory between each exercise group and WTC group(P>0.05).In working memory,the number of errors in ADM group and ADH group was less than that in ADC group(P<0.01),and the number of errors in ADM group and ADH group was also less than that in ADL group(P<0.01).In reference memory,the number of errors in ADM group was less than that in ADC group(P<0.05),ADM group was less than that in ADL group(P<0.01),and ADH group was less than that in ADL group(P<0.05).(4)Immunofluorescence technique: Aβ1-42 was significantly deposited in DG area of hippocampus in ADC group than in WTC group(P<0.01),and DCX was decreased(P<0.05).However,there was no significant difference between the exercise group and WTC group(P>0.05).ADL group and ADH group decreased Aβ1-42(P<0.05)and DCX increased(P<0.05).Aβ1-42 in ADM group was lower than that in ADC group(P<0.01),and Aβ1-42 in ADM group was lower than that in ADL group(P<0.05).The DCX of ADM group was higher than that of ADC and ADL group(P<0.05).(5)Western Blotting technique: Aβ1-42 in ADC group was higher than that in WTC group(P<0.01),and DCX was lower than that in WTC group(P<0.05).ADL and ADH groups were lower than ADC group(P<0.05),ADM group was lower than ADC group(P<0.01),ADM group was lower than ADL group(P<0.05).DCX in ADM group and ADH group was higher than that in ADC group(P<0.05),and also higher than that in ADL group(P<0.05).Conclusion:(1)At the age of 8 months in AD control group,there were obvious hippocampal Aβ deposition and decreased neurogenesis activity,and finally the learning and memory ability was impaired.(2)Low load aerobic exercise can reduce hippocampal Aβ in AD mice.However,it has no significant effect on promoting the migration and differentiation of neural precursor cells and improving the ability of learning and memory.(3)Medium and high load aerobic exercise can not only reduce hippocampal Aβof AD mice,but also promote the migration and differentiation of neural precursor cells and improve the ability of learning and memory.And moderate load aerobic exercise has the best effect.