Brainstem circuits controlling gastrointestinal function

项目总结/摘要 自主神经功能障碍，尤其是胃肠动力障碍，在帕金森病患者中经常发生。 帕金森氏病（PD）是帕金森氏病（Parkinson's disease，PD）的一种常见的临床表现。慢性便秘 和胃排空延迟在许多帕金森病患者中观察到，并且特别麻烦; 后者为吸收和适当的治疗剂量提供了额外的未解决的并发症 L-DOPA方案，即用于治疗PD相关运动功能障碍的主要疗法。 为了阐明帕金森病相关胃轻瘫的治疗方法，有必要 了解导致病因的因素，包括环境影响， 发展为特发性PD。 一些流行病学研究表明，PD的发病率增加与农药或 除草剂暴露和农村地点/生活方式。同样，研究表明，素食者谁遵循 与非素食者相比，植物种子凝集素含量高的饮食具有更高的PD发病率。值得注意的是，一些 东南亚的蔬菜栽培品种富集了高达1%的凝集素浓度。 基于我们的初步研究表明，在给予 亚阈值剂量的凝集素和除草剂百草枯，我们提出了以下新的假设：“凝集素- 介导的环境毒素的逆行运输通过迷走神经依赖性 ENS-DMV-SNpc通路”的作用。去调查这部小说 假设，我们将使用体内光遗传学、电生理学、解剖学和行为学的组合， 研究帕金森病相关的胃相关神经通路影响的啮齿动物方法 胃功能障碍。

Project Summary/Abstract Autonomic dysfunctions, especially gastrointestinal motility disorders, occur frequently in parkinsonian patients and are often prodromic to the clinical diagnosis of Parkinson’s disease (PD). Chronic constipation and delayed gastric emptying are observed in many parkinsonian patients and are especially troublesome; the latter provides an additional unresolved complication to the absorption and appropriate therapeutic dosing regimen of L-DOPA, i.e. the main therapy used to treat PD-related motor dysfunctions. In the quest to elucidate the treatment of parkinsonian-related gastroparesis, it is necessary to understand the factors, including the environmental influences, which contribute to the etiology and development of idiopathic PD. Several epidemiological studies have associated an increased incidence of PD with pesticide or herbicide exposure and rural location/lifestyle. Similarly, studies have indicated that vegetarians who follow a diet high in plant seed lectins have a higher incidence of PD compared to non-vegetarians. Of note, some vegetable cultivars in SE Asia have enriched lectin concentrations of up to 1%. Based on our preliminary studies that indicate impaired gastric motility upon administration of subthreshold doses of lectins and the herbicide paraquat, we propose the following novel hypothesis: “lectin- mediated retrograde transport of environmental toxins disrupts the brain-gut axis through a vagally-dependent ENS-DMV-SNpc pathway” prior to the development of PD-related motor dysfunctions. To investigate this novel hypothesis, we will use a combination of in vivo optogenetic, electrophysiological, anatomical and behavioral approaches in rodents to investigate on the gastric-related neural pathways affected in parkinsonian-related gastric dysfunctions.