Reduced expression of choline acetyltransferase in vagal motoneurons and gastric motor dysfunction in a 6-OHDA rat model of Parkinson's disease

Reduced expression of choline acetyltransferase in vagal motoneurons and gastric motor dysfunction in a 6-OHDA rat model of Parkinson's disease
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帕金森病 6-OHDA 大鼠模型中迷走神经运动神经元胆碱乙酰转移酶表达降低和胃运动功能障碍

DOI:
10.1016/j.brainres.2011.09.006
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发表时间:
2011-10
期刊:
影响因子:
2.9
通讯作者:
Tang, Yuan-yuan
Tang, Yuan-yuan
中科院分区:
医学3区
文献类型:
--
作者:
Zheng, Li-Fei;Zhang, Yue;Zhu, Jin-Xia;Wang, Zhi-Yong;Li, Xiao-feng;Song, Jin;Hong, Feng;Lian, Hui;Wang, Qian;Feng, Xiao-Yan;Tang, Yuan-yuan

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帕金森病(PD)的特征是黑质(SN)多巴胺能神经元变性,伴有迷走神经背侧运动核(DMV)的病理改变。PD患者经常发生胃肠道功能障碍,如胃轻瘫。然而,PD患者出现这些症状的机制尚不清楚。在本研究中,我们研究了在大鼠双侧SN微量注射6-羟基多巴胺(6-OHDA)(简称6-OHDA大鼠)的DMV和胃运动功能的胆碱能和儿茶酚胺能神经元的变化,并探讨了可能的机制。用应变式力传感器记录在体胃运动。胆碱乙酰转移酶(ChAT)和酪氨酸羟化酶(TH)的表达通过免疫荧光和蛋白质印迹分析进行了评价。采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。6-OHDA治疗6周后,DMV ChAT表达减少,TH表达增强,胃肌层Ach含量降低。在6-OHDA大鼠中观察到胃排空延迟和胃动力受损。本研究的结果表明,减少ChAT和TH在DMV的表达增强可能与胃排空延迟和胃动力受损的发展,这可能是部分由于减少从迷走神经Ach释放。
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.
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