Exercise-Upregulated Proteasome Activity On Hippocampus Improves Learning And Memory In Mice

Objective:To observe the change of proteasome activity in mice hippocampus after running wheel, investigate the effects of proteasome on maintaining learning and memory. Methods:The distance of every mouse was monitored by Vital View system. The proteasome activity of different times and areas were detected. At the same time, the learning and memory ability of mice were observed by Y maze spontaneous alternative experiment and step-down experiment. The accumulation of ubiquitinated proteins and PSMB5 were detected by western blotting and q PCR. Then the proteasome inhibitor MG132 was used in this study. The inhibitor was positioning injected into hippocampus(10μg/side) and equal volume of DMSO was injected into the control group. Every mouse of two groups had running wheel in its cage after positioning injection. Then the proteasome activity was detected and the learning and memory ability of mice were observed by Y maze spontaneous alternative experiment and step-down experiment. Results:Proteasome activity assay results demonstrated that with the time of exercise prolonged, the proteasome activity of hippocampus gradually increased and enhanced 33.0 ± 6.3%(P <0.01) by 14 d. However, the proteasome activity of the brain cortex, spinal cord and other parts had no significant difference compared with the sedentary mice. After running wheel exercise for 28 d, the spontaneous alternation frequency of Y- maze in exercise group increased 16.9 ± 4.4%(P <0.05) compared with the control group, and the latency time of step-down avoidance test increased 12.3 ± 4.8 s(P <0.05) compared with the control. The results of western blotting showed that after running wheel exercise for 14 d, the protein level of PSMB5 increased 16.1±3.3% and the accumulation of ubiquitinated proteins was decreased compared with the sedentary group. After positioning injection, Vital View monitoring results showed that the time and distance of running wheel exercise had no significant difference between MG132 group and DMSO group, but the proteasome activity of MG132 group was decreased 34.9 ± 4.9%(P <O.01) compared with DMSO group. The spontaneous alternation frequency of Y- maze in MG132 group(60.0 ± 11.0%) was lower compared with DMSO control group(74.5 ± 7.8%), and the latency time of step-down avoidance test of MG132 group(6.0 ± 1.9s) also showed decreased compared with DMSO group(45.2 ± 17.1s)(P<0.05). Conclusion:(1)Running wheel exercise can upregulated proteasome activity of hippocampus and improve the ability of learning and memory;(2) The proteasome inhibitors downregulated the function of exercise on improving learning and memory;(3) Proteasome activity plays an important role in maintaining learning and memory.