Effects Of Aerobic Exercise On CaMk? In The Central Nervous System Of APP/PS1 Transgenic Mice

Objective: To investigate the effects of aerobic exercise on the cognitive-behavior of6-month-old and 8-month-old APP/PS1 transgenic mice,synaptic numbers and the expression of CaMK?? and P-CaMK?? in cortex and hippocamp.Methods: 60 healthy male 4-month-old APP/PS1 and 60 C57BL/6J mice were randomly divided into two groups(AS,CS,CE,AE).And there was no significant difference between 4 groups.15 of the exercise groups mice participated in 8 weeks treadmill exercise and the remaining 15 mice participated in 16 weeks treadmill exercise,the slope was 0,60min/d,5d/w,and the speed was 15 m /min during the first10 minutes,18 m /min during the following 50 minutes.The behavioral change was detected by step-down fear conditioning,the cortical and hippocampal synaptic numbers were observed by transmission electron microscope(TEM),and the expression of Ca MK?? and P-Ca MK?? were measured by Western Blot.Results:(1)Behaviorally: Compared with the control group,the behaviors of6-month-old APP/PS1 mice changed significantly(P<0.01),and the standard rate was significantly lower(P<0.05).After 8-week aerobic exercise,the mice performed significantly better than AS(P<0.01)and the standard rate was higher.And the behaviors of 8-month-old APP/PS1 mice changed significantly(P<0.01),and the standard rate was significantly lower(P<0.05).After 16-week aerobic exercise,the mice performed significantly better than AS(P<0.01)and the standard rate was higher(P<0.05).(2)Synaptic numbers of 6-month-old APP/PS1 mice in cortex and hippocamp is lower than that in CS(CA1 P<0.05;frontal lobe P<0.01;temporal lobe P<0.01).After 8-week aerobic exercise,synaptic numbers of 6-month-old C57 mice in cortex and hippocamp is higher than that in CS(CA3 P<0.05;frontal lobe P<0.05;temporal lobe P<0.05),and synaptic numbers of 6-month-old APP/PS1 mice in cortex and hippocamp is higher than that in AS(CA1 P<0.01;CA3 P<0.01;frontal lobe P < 0.01;temporal lobe P < 0.01).Synaptic numbers of 8-month-old APP/PS1 mice in cortex and hippocamp is lower than that in CS(CA1 P<0.01;CA3P < 0.01;frontal lobe P < 0.01;temporal lobe P < 0.01).After 16-week aerobic exercise,synaptic numbers of 8-month-old C57 mice in cortex and hippocamp is higher than that in CS(CA1 P < 0.05;CA3 P < 0.01;temporal lobe P < 0.05).Synaptic numbers of 8-month-old APP/PS1 mice in cortex and hippocamp is lower than that in AS(CA1 P<0.01;CA3 P<0.01;frontal lobe P<0.01;temporal lobe P< 0.01).(3)In cortex and hippocamp,compared with the control group,the expression of Ca MK?? decreases significantly in 6-month-old APP/PS1 mice(CA3P<0.01;frontal lobe P<0.01;temporal lobe P<0.01),and the phosphorylation rate of P-Ca MK?? is also lower than CS(CA3 P<0.05;frontal lobe P<0.01;temporal lobe P<0.05).After 8-week aerobic exercise,in hippocamp CA3 region and temporal lobe,the expression of Ca MK?? increases significantly in 6-month-old C57 mice(CA3 P<0.01;temporal lobe P<0.01),while the expression of Ca MK?? decreases significantly in frontal lobe(P<0.01).And the phosphorylation rate of P-Ca MK??is lower than CS(CA1 P<0.01;CA3 P<0.01;frontal lobe P<0.01;temporal lobe P< 0.01).In cortex and hippocamp,the expression of Ca MK ? ? increases significantly in 6-month-old APP/PS1 mice(CA1 P<0.01;CA3 P<0.01;frontal lobe P<0.01;temporal lobe P<0.01),but the phosphorylation rate of P-Ca MK??decreases significantly(CA1 P<0.01;CA3 P<0.01;frontal lobe P<0.01;temporal lobe P < 0.01).Compared with the control group,the expression of Ca MK ? ?decreases significantly in hippocamp CA3 region of 8-month-old APP/PS1 mice(P<0.01),and the phosphorylation rate of P-Ca MK?? decreases significantly in cortex and hippocamp(CA1 P<0.01;CA3 P<0.05;frontal lobe P<0.01;temporal lobe P<0.01).After 16-week aerobic exercise,the expression of Ca MK?? increases in hippocamp of 8-month-old C57 mice,but in frontal lobe and temporal lobe,it decreases.In cortex and hippocamp,the phosphorylation rate of P-Ca MK ? ?decreases significantly compared with CS(CA1 P<0.01;CA3 P<0.05;frontal lobe P < 0.05;temporal lobe P < 0.01).The expression of Ca MK ? ? increases significantly in 8-month-old APP/PS1 mice(CA1 P<0.05;CA3 P<0.01;frontal lobe P<0.05;temporal lobe P<0.01),while the phosphorylation rate of P-Ca MK??decreases significantly compared with AS(CA1 P<0.01;CA3 P<0.01;frontal lobe P<0.05;temporal lobe P<0.01).Conclusion: Aerobic exercise may increase the expression and the activity of CaMK? ?,thus resulting in inhibiting synaptic loss in cortex and hippocamp of6-month-old and 8-month-old APP/PS1 transgenic mice.That may be a molecular mechanism of exercise-induced learning and memory ability promoting.