Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, United States.
Behav Brain Res. 2012 Oct 1;234(2):343-8. doi: 10.1016/j.bbr.2012.07.003. Epub 2012 Jul 14.
In addition to its cardinal symptoms of bradykinesia, muscle rigidity, resting tremor and postural disturbances, Parkinson's disease (PD) also affects orolingual motor function. Orolingual motor deficits can contribute to dysphagia, which increases morbidity and mortality in this population. Previous preclinical studies describing orolingual motor deficits in animal models of PD have focused on unilateral nigrostriatal dopamine (DA) depletion. In this study we compared the effects of unilateral vs bilateral 6-hydroxydopamine (6-OHDA)-induced DA depletion in rats trained to lick water from an isometric force-sensing disc. Rats received either unilateral or bilateral 6-OHDA into the medial forebrain bundle and were tested for four weeks post-lesion. Dependent variables included task engagement (the number of licks per session), tongue force (mean and maximum), and tongue motility (the number of licks per second). While both lesion groups exhibited decreased tongue force output, tongue motility deficits were present in only the group that received unilateral nigrostriatal DA depletion. Task engagement was not significantly diminished by 6-OHDA. Analysis of striatal DA tissue content revealed that DA depletion was ∼97% in the unilateral group and ∼90% in the bilateral group. These results suggest that while nigrostriatal DA depletion affects tongue force output, deficits in tongue motility may instead result from a functional imbalance in neural pathways affecting this midline structure.
除了运动迟缓、肌肉僵硬、静止性震颤和姿势障碍等主要症状外,帕金森病(PD)还会影响口颌运动功能。口颌运动功能障碍可导致吞咽困难,从而增加该人群的发病率和死亡率。先前描述 PD 动物模型中口颌运动功能障碍的临床前研究主要集中在单侧黑质纹状体多巴胺(DA)耗竭上。在这项研究中,我们比较了单侧和双侧 6-羟多巴胺(6-OHDA)诱导的 DA 耗竭对经过训练从等距力感测盘舔水的大鼠的影响。大鼠接受单侧或双侧 6-OHDA 注入内侧前脑束,并在损伤后 4 周进行测试。因变量包括任务参与度(每次试验的舔次数)、舌力(平均值和最大值)和舌运动性(每秒的舔次数)。虽然两组损伤大鼠的舌力输出均降低,但仅单侧黑质纹状体 DA 耗竭组的大鼠出现舌运动性障碍。6-OHDA 对任务参与度没有显著影响。纹状体 DA 组织含量分析表明,单侧组的 DA 耗竭约为 97%,双侧组的 DA 耗竭约为 90%。这些结果表明,虽然黑质纹状体 DA 耗竭会影响舌力输出,但舌运动性障碍可能是由于影响中线结构的神经通路的功能失衡所致。