Henderson J M, Annett L E, Torres E M, Dunnett S B
Department of Experimental Psychology and the MRC Cambridge Centre for Brain Repair, University of Cambridge, UK.
Eur J Neurosci. 1998 Feb;10(2):689-98. doi: 10.1046/j.1460-9568.1998.00077.x.
Recent studies in non-human primates support a role for the subthalamic nucleus in the expression of parkinsonian symptomatology, and it has been proposed that subthalamic lesions may provide a surgical treatment for the symptoms of Parkinson's disease in humans. We have applied a broad range of behavioural tests to characterize the effects of lesions of the subthalamic nucleus on parkinsonian symptoms in the unilateral 6-hydroxydopamine (6-OHDA) lesioned marmoset (Callithrix jacchus). Thirteen marmosets were trained on a battery of behavioural tasks that were conducted at regular intervals before and after surgery. All received unilateral 6-OHDA lesions to the medial forebrain bundle. Seven animals were then given an additional N-methyl-D-aspartate lesion of the ipsilateral subthalamic nucleus, whereas the remaining six animals received a variety of control or sham lesions to the nucleus. The 6-OHDA lesions induced a strong ipsilateral bias in head position; mild-moderate ipsilateral rotation spontaneously and after injection of saline or amphetamine; and contralateral rotation after injection of apomorphine. Hemineglect was evident as delayed initiation of reaches on the contralateral side on the staircase reaching task. Additional subthalamic lesions significantly reversed the bias in head position from ipsilateral to contralateral and decreased neglect as evidenced by improved latencies to initiate reaching on the contralateral side at the staircase. However, deficits in skilled movements persisted in the subthalamic nucleus lesion group in that they did not complete the staircase task any faster than the control group and remained impaired on another task which required reaching into tubes. These behavioural effects demonstrate that excitotoxic lesioning of the subthalamic nucleus can ameliorate some, but not all, parkinsonian-like deficits in the unilateral 6-OHDA lesioned marmoset.
近期对非人类灵长类动物的研究支持丘脑底核在帕金森氏症症状表达中所起的作用，并且有人提出丘脑底核损伤可能为人类帕金森氏病的症状提供一种外科治疗方法。我们应用了广泛的行为测试来描述丘脑底核损伤对单侧6-羟基多巴胺（6-OHDA）损伤的狨猴（绢毛猴）帕金森氏症症状的影响。13只狨猴接受了一系列行为任务的训练，这些任务在手术前后定期进行。所有动物均接受内侧前脑束的单侧6-OHDA损伤。然后，7只动物接受同侧丘脑底核的额外N-甲基-D-天冬氨酸损伤，而其余6只动物接受该核的各种对照或假损伤。6-OHDA损伤导致头部位置强烈的同侧偏向；自发地以及在注射生理盐水或苯丙胺后出现轻度至中度同侧旋转；注射阿扑吗啡后出现对侧旋转。在阶梯式伸手任务中，对侧伸手延迟表明存在半侧忽视。额外的丘脑底核损伤显著地将头部位置的偏向从同侧反转到对侧，并减少了忽视，这表现为在阶梯式任务中对侧伸手启动潜伏期的改善。然而，丘脑底核损伤组在熟练运动方面的缺陷仍然存在，因为它们完成阶梯式任务的速度并不比对照组快，并且在另一项需要伸进管子的任务中仍然受损。这些行为效应表明，丘脑底核的兴奋性毒性损伤可以改善单侧6-OHDA损伤的狨猴中一些但并非全部类似帕金森氏症的缺陷。
