Delayed gastric emptying and enteric nervous system dysfunction in the rotenone model of Parkinson's disease.
Delayed gastric emptying and enteric nervous system dysfunction in the rotenone model of Parkinson's disease.
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DOI：
10.1016/j.expneurol.2009.04.023
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发表时间：
2009-07
影响因子：
5.3
通讯作者：
Srinivasan, Shanthi
中科院分区：
文献类型：
--
作者：
Greene, James G.;Noorian, Ali Reza;Srinivasan, Shanthi
胃肠功能障碍是帕金森病最常见的非运动症状。帕金森病患者胃肠动力障碍的症状包括胃排空延迟引起的早期饱腹感和体重减轻，以及结肠运输受损引起的便秘。由于缺乏对PD动物模型中胃肠道症状和病理学的研究，阻碍了对PD患者这些症状的病理生理学和治疗的了解。我们报道，帕金森病神经毒素和线粒体复合体I抑制剂鱼藤酮在没有重大运动功能障碍或中枢神经系统病理的情况下，长期给药会导致胃排空延迟和肠神经元功能障碍。用渗透压微泵(3 mg/kg/d)注射鱼藤酮22~28d后，45%的大鼠胃排空明显延迟。来自鱼藤酮治疗动物的离体肠神经介导的肌肉收缩的电生理记录证实了与鱼藤酮治疗相关的肠道抑制缺陷。鱼藤酮还导致与体重减轻和食物和水摄入量减少相关的大便频率的一过性下降。病理上，在鱼藤酮处理的动物中，肠神经元数或形态没有明显的变化。这些结果表明，肠抑制神经元可能特别容易受到帕金森神经毒素对线粒体抑制的影响，并为帕金森病胃肠道异常可以在啮齿类动物身上建立模型提供了证据。
Gastrointestinal (GI) dysfunction is the most common non-motor symptom of Parkinson’s disease (PD). Symptoms of GI dysmotility in PD include early satiety and weight loss from delayed gastric emptying and constipation from impaired colonic transit. Understanding the pathophysiology and treatment of these symptoms in PD patients has been hampered by the lack of investigation into GI symptoms and pathology in PD animal models. We report that the parkinsonian neurotoxin and mitochondrial complex I inhibitor rotenone causes delayed gastric emptying and enteric neuronal dysfunction when administered chronically to rats in the absence of major motor dysfunction or CNS pathology. When examined 22–28 days after initiation of rotenone infusion by osmotic minipump (3 mg/kg/day), 45% of rotenone-treated rats had a profound delay in gastric emptying. Electrophysiological recording of neurally-mediated muscle contraction in isolated colon from rotenone-treated animals confirmed an enteric inhibitory defect associated with rotenone treatment. Rotenone also induced a transient decrease in stool frequency that was associated with weight loss and decreased food and water intake. Pathologically, no alterations in enteric neuron numbers or morphology were apparent in rotenone-treated animals. These results suggest that enteric inhibitory neurons may be particularly vulnerable to the effects of mitochondrial inhibition by parkinsonian neurotoxins and provide evidence that parkinsonian gastrointestinal abnormalities can be modeled in rodents.
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影响因子：
4.3
作者：
Bolanos, Juan P.;Delgado-Esteban, Maria;Almeida, Angeles
通讯作者：
Almeida, Angeles
DOI：
10.1152/ajpgi.00317.2007
发表时间：
2007-11-01
影响因子：
4.5
作者：
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作者：
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作者：
Fleming, SM;Zhu, CN;Chesselet, MF
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Chesselet, MF
影响因子：
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作者：
Antonio Cabezos, Pablo;Vera, Gema;Abalo, Raquel
通讯作者：
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