Differential sensitivity of cranial and limb motor function to nigrostriatal dopamine depletion.
Differential sensitivity of cranial and limb motor function to nigrostriatal dopamine depletion.
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DOI：
10.1016/j.bbr.2012.09.031
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发表时间：
2013-01-15
影响因子：
2.7
通讯作者：
Kleim, Jeffrey A.
中科院分区：
文献类型：
--
作者：
Plowman, Emily K.;Maling, Nicholas;Rivera, Benjamin J.;Larson, Krista;Thomas, Nagheme J.;Fowler, Stephen C.;Manfredsson, Fredric P.;Shrivastav, Rahul;Kleim, Jeffrey A.
本研究确定了单侧纹状体多巴胺耗竭对颅运动与肢体运动功能的不同影响。40只雄性Long Evans大鼠首先在一个综合的运动测试电池上训练，该电池分离了颅骨与肢体运动功能，包括：圆柱体前爪放置、单颗粒到达、粉丝面食处理、向日葵籽打开、面食咬声和舔任务。在基线测试后，将动物随机分配至6-羟基多巴胺（6-OHDA）（n = 20）或对照组（n = 20）。6-OHDA组动物接受单侧纹状体内6-OHDA输注以诱导纹状体多巴胺耗竭。输注后6周，对所有动物进行相同的运动试验。近红外光密度测定法进行切片通过纹状体，酪氨酸羟化酶（TH）的化学染色。6-OHDA条件下的动物显示TH染色平均减少88.27%。尽管6-OHDA动物在所有运动任务上均显著受损，但肢体运动缺陷比颅骨运动障碍更严重。此外，肢体运动任务的性能与TH耗竭的程度相关，而颅运动障碍的性能没有显着的相关性。这些结果表明，肢体运动功能可能比颅运动功能对纹状体多巴胺能耗竭更敏感，并且与针对帕金森病中黑质纹状体多巴胺能系统的治疗对肢体运动症状比颅运动障碍更有效的临床观察一致。
The present study determined the differential effects of unilateral striatal dopamine depletion on cranial motor versus limb motor function. Forty male Long Evans rats were first trained on a comprehensive motor testing battery that dissociated cranial versus limb motor function and included: cylinder forepaw placement, single pellet reaching, vermicelli pasta handling; sunflower seed opening, pasta biting acoustics, and a licking task. Following baseline testing, animals were randomized to either a 6-hydroxydopamine (6-OHDA) (n = 20) or control (n = 20) group. Animals in the 6-OHDA group received unilateral intrastriatal 6-OHDA infusions to induce striatal dopamine depletion. Six-weeks following infusion, all animals were re-tested on the same battery of motor tests. Near infrared densitometry was performed on sections taken through the striatum that were immunohistochemically stained for tyrosine hydroxylase (TH). Animals in the 6-OHDA condition showed a mean reduction in TH staining of 88.27%. Although 6-OHDA animals were significantly impaired on all motor tasks, limb motor deficits were more severe than cranial motor impairments. Further, performance on limb motor tasks was correlated with degree of TH depletion while performance on cranial motor impairments showed no significant correlation. These results suggest that limb motor function may be more sensitive to striatal dopaminergic depletion than cranial motor function and is consistent with the clinical observation that therapies targeting the nigrostriatal dopaminergic system in Parkinson’s disease are more effective for limb motor symptoms than cranial motor impairments.
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