Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Brain Res. 2011 Oct 28;1420:59-67. doi: 10.1016/j.brainres.2011.09.006. Epub 2011 Sep 9.
Parkinson's disease (PD) has been characterized by dopaminergic neuron degeneration in the substantia nigra (SN) accompanied by pathology of the dorsal motor nucleus of the vagus (DMV). PD patients have often experienced gastrointestinal dysfunctions, such as gastroparesis. However, the mechanism underlying these symptoms in PD patients is not clear. In the present study, we investigated alterations of cholinergic and catecholaminergic neurons in the DMV and gastric motor function in rats microinjected with 6-hydroxydopamine (6-OHDA) bilaterally into the SN (referred to as 6-OHDA rats) and explored possible mechanisms. A strain gauge force transducer was used to record gastric motility in vivo. Expression of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) was evaluated by immunofluorescence and western blot analysis. Acetylcholine (Ach) content was measured using ultra-performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS) analysis. After treatment with 6-OHDA for 6weeks, 6-OHDA rats exhibited decreased ChAT and enhanced TH expression in the DMV and decreased Ach content in the gastric muscular layer. Delayed gastric emptying and impaired gastric motility in vivo were observed in 6-OHDA rats. The results of the present study indicated that decreased ChAT and enhanced TH expression in the DMV may be correlated with the development of delayed gastric emptying and impaired gastric motility, which may be partly due to the decreased Ach release from the vagus.
帕金森病（PD）的特征是黑质（SN）中的多巴胺能神经元退化，伴有迷走神经背核（DMV）的病理学改变。PD 患者常经历胃肠道功能障碍，如胃轻瘫。然而，PD 患者这些症状的机制尚不清楚。在本研究中，我们研究了双侧 SN 内注射 6-羟多巴胺（6-OHDA）的大鼠 DMV 中的胆碱能和儿茶酚胺能神经元的变化以及胃运动功能，并探讨了可能的机制。使用应变计力换能器在体内记录胃动力。通过免疫荧光和 Western blot 分析评估胆碱乙酰转移酶（ChAT）和酪氨酸羟化酶（TH）的表达。使用超高效液相色谱串联质谱（UPLC/MS/MS）分析测定乙酰胆碱（Ach）含量。在 6-OHDA 处理 6 周后，6-OHDA 大鼠在 DMV 中表现出 ChAT 减少和 TH 表达增强，胃肌层 Ach 含量减少。在 6-OHDA 大鼠中观察到胃排空延迟和胃运动功能障碍。本研究的结果表明，DMV 中 ChAT 减少和 TH 表达增强可能与胃排空延迟和胃运动功能障碍的发展有关，这可能部分归因于迷走神经释放的 Ach 减少。
