Endurance exercise promotes cardiorespiratory rehabilitation without neurorestoration in the chronic mouse model of Parkinsonism with severe neurodegeneration
Endurance exercise promotes cardiorespiratory rehabilitation without neurorestoration in the chronic mouse model of Parkinsonism with severe neurodegeneration
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DOI：
10.1016/j.neuroscience.2007.07.038
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发表时间：
2007-10-12
期刊：
影响因子：
3.3
通讯作者：
Lau, Y.-S.
中科院分区：
文献类型：
--
作者：
Al-Jarrah, M.;Pothakos, K.;Lau, Y.-S.
尽管一些临床和实验室报告表明，运动可能会产生神经保护作用，并恢复多巴胺能和运动功能，但耐力运动对帕金森病患者的身体康复作用尚未得到很好的确立。本研究采用慢性帕金森病小鼠模型，给雄性C57BL/6小鼠注射1-甲基-4-苯基-1，2，3，6-四氢吡啶(25 mg/kg)和丙磺舒(250 mg/kg)，共5周。这种慢性帕金森病模型表现出黑质纹状体神经元严重和持续的丢失，导致小鼠严重的多巴胺耗竭和运动障碍。诱导帕金森病后，这些小鼠能够在电动跑步机上以18m/min的速度、0度倾斜、40min/d、每周5天的速度进行为期4周的运动训练。在运动训练结束时，我们检查并比较了他们的心肺功能、行为和神经化学变化与丙磺舒治疗的对照组和久坐不动的帕金森病小鼠的变化。慢性帕金森病小鼠运动后4周的静息心率明显低于运动前，而对照组和久坐不动的帕金森病小鼠运动前和运动后4周的静息心率无明显变化。运动帕金森病小鼠也能从4周不运动的帕金森病小鼠的心电图R波幅升高中恢复过来。在Bruce最大运动激发试验前和期间，运动帕金森病小鼠的氧耗量、二氧化碳产生和体热产生值均显著低于安静小鼠。此外，运动帕金森病小鼠的心脏左心室重量更大，骨骼肌中柠檬酸合成酶的活性水平也增加。安非他明诱导的依赖多巴胺释放的运动活动在久坐的帕金森病小鼠中显著受到抑制，在运动帕金森病鼠中也受到抑制。最后，重度帕金森病小鼠运动后黑质纹状体酪氨酸羟化酶表达和多巴胺水平的丧失对神经元的恢复并不明显。综上所述，这些数据表明，4周的跑步机运动提高了身体耐力，导致慢性帕金森病小鼠的心肺和代谢适应，这些小鼠患有严重的神经变性，但没有表现出黑质纹状体多巴胺能功能的恢复潜力。(C)2007年IBRO。爱思唯尔有限公司出版。保留所有权利。
Physical rehabilitation with endurance exercise for patients with Parkinson's disease has not been well established, although some clinical and laboratory reports suggest that exercise may produce a neuroprotective effect and restore dopaminergic and motor functions. In this study, we used a chronic mouse model of Parkinsonism, which was induced by injecting male C57BL/6 mice with 10 doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg) and probenecid (250 mg/kg) over 5 weeks. This chronic parkinsonian model displays a severe and persistent loss of nigrostriatal neurons, resulting in robust dopamine depletion and locomotor impairment in mice. Following the induction of Parkinsonism, these mice were able to sustain an exercise training program on a motorized rodent treadmill at a speed of 18 m/min, 0 degrees of inclination, 40 min/day, 5 days/week for 4 weeks. At the end of exercise training, we examined and compared their cardiorespiratory capacity, behavior, and neurochemical changes with that of the probenecid-treated control and sedentary parkinsonian mice. The resting heart rate after 4 weeks of exercise in the chronic parkinsonian mice was significantly lower than the rate before exercise, whereas the resting heart rate at the beginning and 4 weeks afterward in the control or sedentary parkinsonian mice was unchanged. Exercised parkinsonian mice also recovered from elevated electrocardiogram R-wave amplitude that was detected in the parkinsonian mice without exercise for 4 weeks. The values of oxygen consumption, carbon dioxide production, and body heat generation in the exercised parkinsonian mice before and during the Bruce maximal exercise challenge test were all significantly lower than that of their sedentary counterparts. Furthermore, the exercised parkinsonian mice demonstrated a greater mass in the left ventricle of the heart and an increased level of citrate synthase activity in the skeletal muscles. The amphetamine-induced, dopamine release-dependent locomotor activity was markedly inhibited in the sedentary parkinsonian mice and was also inhibited in the exercised parkinsonian mice. Finally, neuronal recovery from the loss of nigrostriatal tyrosine hydroxylase expression and dopamine levels in the severe parkinsonian mice after exercise was not evident. Taken all together, these data suggest that 4 weeks of treadmill exercise promoted physical endurance, resulting in cardiorespiratory and metabolic adaptations in the chronic parkinsonian mice with severe neurodegeneration without demonstrating a restorative potential for the nigrostriatal dopaminergic function. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.