Howells Fleur M, Russell Vivienne A, Mabandla Musa V, Kellaway Lauriston A
Division of Physiology, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory 7925, Room 5.02, Anatomy Building, South Africa.
Behav Brain Res. 2005 Dec 7;165(2):210-20. doi: 10.1016/j.bbr.2005.06.044. Epub 2005 Sep 12.
Parkinson's disease (PD) is a progressive neurodegenerative disease of nigrostriatal dopamine (DA) neurons that project from the substantia nigra pars compacta (SNc) to the striatum. To further understand PD, researchers have developed standardized animal models of PD. In this study, Long Evans (LE) rats were unilaterally lesioned by injection of the neurotoxin, 6-hydroxydopamine (6-OHDA), into the medial forebrain bundle (MFB) of the left hemisphere. The rats were divided into three groups randomly; group 1 (runners) were housed in individual cages with attached running wheels, group 2 (stressed-runners) had access to individual free running wheels, except post-lesion when the rats were subjected to immobilization of the running wheel for 1 h per day for 14 days, as well as one session of 24-h food deprivation and a 7-h shift in the light/dark cycle. Group 3 (non-runnners) were housed individually in cages with attached running wheels that were permanently immobilized. Subcutaneous injection of the DA agonist, apomorphine, caused stressed-runners and non-runners to rotate vigorously away from the side of the lesion (contralaterally). Apomorphine-induced rotations provide a behavioural measure of the extent of the lesion, a depletion of more than 80% of DA neurons is required to produce vigorous contralateral rotations in response to apomorphine injection. Runners rotated significantly less than non-runners and stressed-runners. The number of rotations performed by stressed-runners was not significantly different from non-runners, suggesting that stress had cancelled the neuroprotective effect of running. Immunohistochemical staining for tyrosine hydroxylase in the SNc revealed slightly less destruction of DA neurons in the runners than in stressed-runners or non-runners, although these differences did not achieve statistical significance. The behavioural results confirm a previous finding suggesting that voluntary exercise is neuroprotective. A novel finding is that mild stressors cancel the neuroprotection afforded by voluntary exercise.
帕金森病（PD）是一种黑质纹状体多巴胺（DA）神经元的进行性神经退行性疾病，这些神经元从黑质致密部（SNc）投射到纹状体。为了进一步了解帕金森病，研究人员开发了标准化的帕金森病动物模型。在本研究中，通过向左侧大脑前束（MFB）注射神经毒素6-羟基多巴胺（6-OHDA），对Long Evans（LE）大鼠进行单侧损伤。将大鼠随机分为三组；第1组（跑步组）饲养在带有连接跑轮的单独笼子里，第2组（应激跑步组）可以使用单独的自由跑轮，但在损伤后，大鼠每天被固定在跑轮上1小时，持续14天，同时进行一次24小时食物剥夺和7小时的昼夜循环转换。第3组（非跑步组）单独饲养在带有永久固定跑轮的笼子里。皮下注射DA激动剂阿扑吗啡会导致应激跑步组和非跑步组大鼠剧烈地向远离损伤侧（对侧）旋转。阿扑吗啡诱导的旋转提供了损伤程度的行为测量指标，需要耗尽超过80%的DA神经元才能在注射阿扑吗啡后产生剧烈对侧旋转。跑步组大鼠的旋转明显少于非跑步组和应激跑步组。应激跑步组大鼠的旋转次数与非跑步组没有显著差异，这表明应激抵消了跑步的神经保护作用。SNc中酪氨酸羟化酶的免疫组织化学染色显示，跑步组DA神经元的破坏略少于应激跑步组或非跑步组，尽管这些差异没有达到统计学意义。行为学结果证实了先前的一项发现，即自愿运动具有神经保护作用。一个新的发现是，轻度应激源会抵消自愿运动提供的神经保护作用。
