Department of Psychology, University of Gothenburg, Box 500, SE-40350 Gothenburg, Sweden.
Neurotox Res. 2012 Feb;21(2):210-21. doi: 10.1007/s12640-011-9261-z. Epub 2011 Aug 10.
In two experiments, MPTP was administered to C57/BL6 mice according to a single-dose weekly regime (MPTP: 1 × 30 mg/kg on the fifth day of the week, Friday, over 4 weeks) with vehicle group (Vehicle: 1 × 5 ml/kg) treated concurrently. Exercise schedules (delayed) were introduced either at the beginning of the week after the second MPTP injection (MPTP + Exercise(2) group), or at the beginning of the week after the fourth MPTP injection (MPTP + Exercise(4) group). Wheel-running was provided on the first 4 days of each week (Monday-Thursday) more than 30-min periods. In Experiment I, wheel-running exercise was introduced either after 2 or 4 weeks after MPTP/Vehicle. MPTP and Vehicle groups not provided access to the running wheels were placed in single cages within the wheel-running room over 30-min concomitantly with the wheel-running groups. In Experiment II, wheel-running exercise was introduced 2 weeks after MPTP/Vehicle but a no-exercise control group with non-revolving wheel included (MPTP-Wheel). In both experiments, spontaneous motor activity tests during 60-min intervals were performed at the end (Fridays) of weeks 1, 2, 3, 4, 6, 8, and 10, where the week on which the first injection of MPTP was the first week; in the case of weeks 1-4, this was immediately before MPTP/Vehicle injections. It was observed that the introduction of the exercise schedule after the second MPTP injection, but not after the fourth injection, restored motor activity that had been markedly elevated by the end of the tenth week. Subthreshold administration of L-dopa tests was performed after the spontaneous motor activity tests 6, 8 and 10; these indicated significant effects of exercise, MPTP + Exercise(2) group, on Tests 6 and 8, but not Test 10. The physical exercise schedule in that group also showed markedly attenuated loss of dopamine (DA). Restoration of MPTP-induced motor activity deficits and DA loss was a function of the point at which exercise was introduced, in the present case after two administrations of the neurotoxin. In Experiment II, physical exercise markedly attenuated the hypokinesic effect of MPTP in the exercise condition, MPTP-exercise, but not in the non-exercise conditions, MPTP-Cage and MPTP-Wheel, for both spontaneous motor activity and L-dopa-induced activity. MPTP-induced loss of DA was also attenuated by exercise.
在两项实验中，根据每周单次剂量方案（MPTP：每周五第 5 天给予 1×30mg/kg，共 4 周）向 C57/BL6 小鼠给予 MPTP，同时给予载体组（载体：1×5ml/kg）。运动方案（延迟）在第二次 MPTP 注射后（MPTP+Exercise(2)组）或第四次 MPTP 注射后（MPTP+Exercise(4)组）的本周开始时引入。每周一至周四提供超过 30 分钟的轮跑运动。在实验 I 中，在 MPTP/Vehicle 后 2 或 4 周引入轮跑运动。未提供轮跑机会的 MPTP 和载体组被放置在轮跑室中的单笼中，与轮跑组同时进行 30 分钟的轮跑。在实验 II 中，在 MPTP/Vehicle 后 2 周引入轮跑运动，但包括无运动对照组（MPTP-Wheel），该组不旋转车轮。在这两项实验中，在第 1、2、3、4、6、8 和 10 周的周五结束时进行 60 分钟间隔的自发运动测试，其中第一周是第一次给予 MPTP 的周；在第 1-4 周的情况下，这是在给予 MPTP/Vehicle 之前立即进行的。结果观察到，在第二次 MPTP 注射后而不是第四次注射后引入运动方案，恢复了第十周末显著升高的运动活动。在自发运动测试 6、8 和 10 后进行亚阈值 L-多巴测试；这些测试表明运动对 MPTP+Exercise(2)组的测试 6 和 8 有显著影响，但对测试 10 没有影响。该组的体育锻炼计划还显示出多巴胺（DA）明显减少。在本研究中，在两次神经毒素给药后，运动方案恢复了 MPTP 诱导的运动活动缺陷和 DA 丢失，这是运动方案引入的时间点的功能。在实验 II 中，运动显著减弱了运动条件下 MPTP 的运动减少作用，即运动条件下的 MPTP-Exercise，但在非运动条件下，即 MPTP-Cage 和 MPTP-Wheel，对自发运动和 L-多巴诱导的运动均如此。运动也减弱了 MPTP 诱导的 DA 丢失。
