O'Dell S J, Gross N B, Fricks A N, Casiano B D, Nguyen T B, Marshall J F
Department of Neurobiology and Behavior, 1452 McGaugh Hall, University of California, Irvine, Irvine, CA 92697, USA.
Neuroscience. 2007 Feb 9;144(3):1141-51. doi: 10.1016/j.neuroscience.2006.10.042. Epub 2006 Dec 8.
Forced use of the forelimb contralateral to a unilateral injection of the dopaminergic neurotoxin 6-hydroxydopamine can promote recovery of motor function in that limb and can significantly decrease damage to dopamine terminals. The present study was conducted to determine (1) whether a form of voluntary exercise, wheel running, would improve motor performance in rats with such lesions, and (2) whether any beneficial effects of wheel running are attributable to ameliorating the dopaminergic damage. In experiment 1, rats were allowed to run in exercise wheels or kept in home cages for 2 1/2 weeks, then given stereotaxic infusions of 6-hydroxydopamine into the left striatum. The rats were replaced into their original environments (wheels or home cages) for four additional weeks, and asymmetries in forelimb use were quantified at 3, 10, 17, and 24 days postoperatively. After killing, dopaminergic damage was assessed by both quantifying 3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid methyl ester ([(125)I]RTI-55) binding to striatal dopamine transporters and counting tyrosine hydroxylase-positive cells in the substantia nigra. Exercised 6-hydroxydopamine-infused rats showed improved motor outcomes relative to sedentary lesioned controls, effects that were most apparent at postoperative days 17 and 24. Despite this behavioral improvement, 6-hydroxydopamine-induced loss of striatal dopamine transporters and tyrosine hydroxylase-positive nigral cells in exercised and sedentary groups did not differ. Since prior studies suggested that forced limb use improves motor performance by sparing nigrostriatal dopaminergic neurons from 6-hydroxydopamine damage, experiment 2 used a combined regimen of forced plus voluntary wheel running. Again, we found that the motor performance of exercised rats improved more rapidly than that of sedentary controls, but that there were no differences between these groups in the damage produced by 6-hydroxydopamine. It appears that voluntary exercise can facilitate recovery from partial nigrostriatal injury, but it does so without evident sparing of dopamine nerve terminals.
单侧注射多巴胺能神经毒素6-羟基多巴胺后，强迫使用对侧前肢可促进该肢体运动功能的恢复，并能显著减少多巴胺能终末的损伤。本研究旨在确定：（1）一种自愿运动形式，即轮转跑步，是否能改善此类损伤大鼠的运动表现；（2）轮转跑步的任何有益效果是否归因于减轻多巴胺能损伤。在实验1中，大鼠被允许在运动轮中跑步或饲养在笼中2.5周，然后将6-羟基多巴胺立体定位注入左侧纹状体。大鼠放回原来的环境（运动轮或笼中）再饲养4周，并在术后第3、10、17和24天对前肢使用的不对称性进行量化。处死大鼠后，通过量化3β-(4-碘苯基)托烷-2β-羧酸甲酯（[(125)I]RTI-55）与纹状体多巴胺转运体的结合以及计数黑质中酪氨酸羟化酶阳性细胞来评估多巴胺能损伤。与久坐不动的损伤对照组相比，经6-羟基多巴胺处理且运动的大鼠运动结果有所改善，这种效果在术后第17天和第24天最为明显。尽管有这种行为改善，但运动组和久坐组中6-羟基多巴胺诱导的纹状体多巴胺转运体丢失和酪氨酸羟化酶阳性黑质细胞数量并无差异。由于先前的研究表明，强迫肢体使用可通过使黑质纹状体多巴胺能神经元免受6-羟基多巴胺损伤来改善运动表现，实验2采用了强迫加自愿轮转跑步的联合方案。同样，我们发现运动大鼠的运动表现比久坐对照组改善得更快，但在6-羟基多巴胺造成的损伤方面，这些组之间没有差异。看来自愿运动可以促进部分黑质纹状体损伤后的恢复，但这样做并未明显保护多巴胺神经终末。
