Role of enteric nervous system homeostasis in gut-nervous system immune signaling

肠神经系统稳态在肠道神经系统免疫信号传导中的作用

• 批准号: 516179478
• 负责人: Professor Dr. Christoph Becker
• 金额: --
• 依托单位: Institut für Biochemie
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/516179478?language=en
• 关键词: Role; enteric; nervous; system; homeostasis

Patients with inflammatory bowel disease (IBD) are more frequently affected by neuropsychiatric, -degenerative and -immunological disorders. It is hypothesized that the co-morbidities of IBD with central nervous system (CNS) diseases reflect communication between the gut and the brain, but the mechanistic underpinnings of this communication remain largely unknown. The enteric nervous system (ENS) is anatomically and functionally connected to the gut and the brain and constitutes a candidate gateway for gut-brain communication. Our preliminary data demonstrate that intestinal inflammation is associated with pronounced ENS remodeling and increased innervation of the inflamed mucosa. Here we investigate the hypothesis that ENS homeostasis under steady-state and pathological conditions depends on the generation of new neurons and that disruption of ENS neurogenesis contributes to IBD and mediate pathological signals from the gut to the CNS. We will investigate this hypothesis through the in-depth histological, molecular and cell biological characterization of sophisticated transgenic mouse models in the context of different experimental IBD models. Results from this study are expected to uncover a novel layer of complexity in the role of the ENS in gut-brain communication.

炎症性肠病(IBD)患者更容易受到神经精神、退行性疾病和免疫疾病的影响。据推测，IBD与中枢神经系统(CNS)疾病的共病反映了肠道和大脑之间的沟通，但这种沟通的机制基础在很大程度上仍不清楚。肠道神经系统(ENS)在解剖和功能上与肠道和大脑相连，是肠道-大脑沟通的候选通道。我们的初步数据表明，肠道炎症与明显的ENS重塑和炎症黏膜神经支配的增加有关。在这里，我们研究了一种假设，即稳态和病理条件下的ENS动态平衡依赖于新神经元的生成，以及ENS神经发生的破坏导致IBD并将病理信号从肠道传递到中枢神经系统。我们将在不同的实验性IBD模型的背景下，通过对复杂的转基因小鼠模型进行深入的组织学、分子和细胞生物学特征来研究这一假说。这项研究的结果有望揭示ENS在肠道-大脑交流中作用的一个新的复杂性层。