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）患者更频繁地受到神经精神病， - 基因和 - 免疫学疾病的影响。假设IBD与中枢神经系统（CNS）疾病的合并症反映了肠道与大脑之间的交流，但是这种交流的机械基础仍然很少知道。肠神经系统（ENS）在解剖学和功能上与肠道和大脑相连，并且构成了肠道通信的候选门户。我们的初步数据表明，肠道炎症与发炎粘膜的明显ENS重塑和增加的神经支配有关。在这里，我们研究了一个假设，即在稳态和病理条件下ENS稳态取决于新神经元的产生，而ENS神经发生的破坏有助于IBD并介导从肠道到CNS的病理信号。我们将通过在不同的实验IBD模型的背景下，通过深入的组织学，分子和细胞生物学表征研究这一假设。这项研究的结果预计将发现ENS在肠道交流中的作用中的新颖复杂性。