Long-term Exercise Increases The Proteasome Activity Of Hippocampus And Ameliorates Neurogenesis In Aged Mice

Objective:In order to further clarify the role of proteasome in neurogenesis process, we observed whether long-term exercise influence on the proteasome activity in hippocampus of aged mice,and the capability of learning and memory. Then we explored the mechanism of delaying the ageing process. It will provide a new strategy about preventing age related degenerative diseases.Methods:In the present study,the newborn mice(Postnantal day 0, P0), adult mice(Postnantal day 90, P90) and aged mice(Postnantal day 540, P540) mice were selected to observe the changes of proteasome activity in the hippocampus at different ages. Isolate hippocampal tissue and apply fluorescence spectrophotometry to detectthe proteasome activity in hippocampus of mice.The P330 mice were selected, establishing a voluntary running wheel model, and the change of hippocampus proteasome activity was observed after running 6 months; Then DCX immunofluorescence staining was used to observe the hippocampal neurogenesis in aged mice; the spontaneous alternation frequency of Y-maze and novel arm experiment were used to observe the ability of learning, memory and space exploration; tail suspention test was used to observe depressed and desperate moods in aged mice.Results:Proteasome activity assay results demonstrate that as time goes on, the proteasome activity of hippocampus gradually decreased,which of P90 and P540 group respectively decreased41.41 ± 6.83% and 43.83 ± 6.62% compared with P0 group(p<0.01); but there was no significant difference between P90 group and P540 group. After running 6 months,the hippocampal proteasome activity of the running wheel group in 11-month-old Balb / c miceincreased to 1.56 ± 0.15 times than that of the control group(p<0.05); Then the results of DCX(early neuronal marker) immunofluorescence staining showed that average outgrouth length of hippocampal newborn neuron in running wheel group was111.69±9.13μm, higherthanthat of the control group(27.75±5.57μm)(p<0.01); The number of DCX positive cells in the Running wheel group was 12.29 ± 2.72, which was8.14 ± 2.36 in the control group(p> 0.05).The alternation of Y-maze in the running wheel group was 65.84±3.01%, and in the control group it was 40.39±5.86%(p<0.05); In novel arm test, running wheel group in the new arm moving distance percentage of the total moving distance is 58.2± 7.58%,higher than that ofcontrol group.The residence time in the novel arm of running wheel group was 147.81 ± 21.59 s, and the residence time in the novel arm of control group was 46.65 ± 15.33 s(p<0.01); Immobility duration time in tail suspention test of the running wheel group was 84.42±26.80 s,and in the control group it was 211.85±24.39 s(p<0.01).Conclusion:The proteasome activity in hippocampus of adult and aged mice were significantly decreased compared with newborn mice. After 6 months of wheel running, the proteasome activity of P330 mice in hippocampusincreased significantlythan that of control group.The length of newborn neurite in DG region extended. Then learning and memory ability of running wheel group mice increased, suggesting that long-term exercise might be helpful to maintain proteasome activity in hippocampus, thereby improving hippocampal neurogenesis in aged mice.