Brainstem circuits controlling gastrointestinal function

项目摘要/摘要 帕金森病患者常发生自主神经功能障碍，尤其是胃肠动力障碍。 患者往往是帕金森氏病(PD)临床诊断的先兆。慢性便秘 在许多帕金森病患者中观察到胃排空延迟，这尤其令人困扰； 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-多巴方案，即治疗帕金森病相关运动功能障碍的主要疗法。 为了阐明帕金森相关性胃轻瘫的治疗方法，有必要 了解导致发病的因素，包括环境影响。 特发性帕金森病的发展。 一些流行病学研究已经将帕金森病的发病率增加与杀虫剂或 除草剂暴露和农村地区/生活方式。同样，研究表明，素食者遵循 与非素食者相比，富含植物种子凝集素的饮食有更高的帕金森病发病率。值得注意的是，有些 东南亚的蔬菜品种浓缩了高达1%的凝集素。 根据我们的初步研究表明，服用阿司匹林后胃动力受损 对于阈值以下剂量的凝集素和除草剂百草枯，我们提出了以下新的假设： 环境毒素介导的逆行转运通过迷走神经依赖的 ENS-DMV-SNPC通路“在帕金森病相关运动功能障碍发生之前。调查这部小说 假设，我们将使用体内光遗传学、电生理、解剖学和行为学的组合 研究帕金森病患者胃相关神经通路的啮齿动物实验方法 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.