Functional and neurochemical changes of the gastrointestinal tract in a rodent model of Parkinson's disease
Functional and neurochemical changes of the gastrointestinal tract in a rodent model of Parkinson's disease
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DOI：
10.1016/j.neulet.2009.10.035
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发表时间：
2009-12-31
影响因子：
2.5
通讯作者：
Tonini, M.
中科院分区：
文献类型：
--
作者：
Blandini, F.;Balestra, B.;Tonini, M.
帕金森病患者出现运动障碍，常伴有外周自主神经功能障碍，包括胃肠道疾病，如吞咽困难、胃瘀和便秘。虽然肠道自主神经功能障碍的机制尚不清楚，但它们可能涉及肠道多巴胺能和/或氮能系统。在本研究中，我们证明，与假手术对照组相比，黑质纹状体多巴胺能神经元单侧6-羟多巴胺损伤的大鼠的推进性活动明显受到抑制，在观察的第四周，每天的粪便排出量减少了60%。免疫组织化学数据显示，6-羟多巴胺处理不影响回肠和结肠近端和远端HuC/ d阳性肌肠神经元的总数。相反，在回肠远端和结肠近端，氮能神经元的数量明显减少。这些结果表明，远端肠道运输紊乱，使人联想到临床上的便秘，可能是推进动力减少的结果，可能是由于在蠕动过程中一氧化氮介导的下降抑制功能受损。2009爱思唯尔爱尔兰有限公司版权所有。
Patients with Parkinson's disease develop motor disturbances often accompanied by peripheral autonomic dysfunctions, including gastrointestinal disorders, such as dysphagia, gastric stasis and constipation. While the mechanisms subserving enteric autonomic dysfunctions are not clearly understood, they may involve the enteric dopaminergic and/or nitrergic systems. In the present study, we demonstrate that rats with unilateral 6-hydroxydopamine lesion of nigrostriatal dopaminergic neurons develop a marked inhibition of propulsive activity compared to sham-operated controls, as indicated by a 60% reduction of daily fecal output at the 4th week of observation. Immunohistochemical data revealed that 6-hydroxydopamine treatment did not affect the total number of HuC/D-positive myenteric neurons in both the proximal and distal segments of ileum and colon. Conversely, in the distal ileum and proximal colon the number of nitrergic neurons was significantly reduced. These results suggest that a disturbed distal gut transit, reminiscent of constipation in the clinical setting, may occur as a consequence of a reduced propulsive motility, likely due to an impairment of a nitric oxide-mediated descending inhibition during peristalsis. (C) 2009 Elsevier Ireland Ltd. All rights reserved.