Myenteric Neuroplasticity Due to Experimental Colitis

实验性结肠炎引起的肌间神经可塑性

• 批准号: 6524630
• 负责人: David R. Linden
• 金额: $ 4.62万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6524630
• 关键词: colitis; electrophysiology; gastrointestinal motility /pressure; gastrointestinal pharmacology; guinea pigs; immunocytochemistry; inflammation; myenteric plexus; neural plasticity; neuroimmunomodulation; organ culture; sulfonate; visceral afferent nerve

DESCRIPTION (provided by applicant): The motor disturbances that are present during inflammation of the bowel reflect a significant interaction between inflammatory mediators and the enteric nervous system. The neural mechanisms of inflammation-induced dysmotility are currently unknown. Using a guinea pig model of experimental colitis, the specific aims of this proposal are to test two hypotheses. The first hypothesis is that inflammation causes an increased excitability in intrinsic primary afferent neurons, which leads to an imbalance in the peristaltic reflex circuit. This hypothesis will be explored by addressing two questions: 1) Do the electrical or synaptic properties of functionally identified myenteric neurons change during experimental colitis? 2) Is the neurogenic propulsive motor activity of the intact guinea pig colon altered during inflammation? The second hypothesis is that changes in the peristaltic reflex circuit, induced by inflammation, persist following histopathological recovery. To test this hypothesis two question will be addressed: 1) Do changes in the electrical or synaptic properties functionally identified myenteric neurons persist or arise following histological recovery from inflammation: 2) Do changes to the neurogenic propulsive motor activity of the intact colon persist or arise following recovery from inflammation? In conducting these studies, we will implement integrated combinations of techniques, including intracellular recording and labeling of neurons, retrograde axonal tracing, immunohistochemistry, and motility assays. These results will advance our understanding of the mechanisms of neuro-immune integration and motility disturbances associated with inflammatory bowel disease and functional bowel disorders.

描述（由申请人提供）：存在的电机干扰 在肠炎期间，肠道反映了 炎症介质和肠神经系统。神经机制 炎症引起的运动障碍目前尚不清楚。使用豚鼠 实验性结肠炎的模型，该提案的具体目的是测试 两个假设。第一个假设是炎症会导致增加 内在原发性传入神经元的兴奋性，导致失衡 在蠕动反射电路中。这个假设将由 解决两个问题：1） 在实验性结肠炎过程中，功能上鉴定出肌植物神经元会发生变化吗？ 2）是完整的豚鼠结肠的神经源性推进运动活性 在炎症期间改变？第二个假设是 由炎症引起的蠕动反射电路持续存在 组织病理学恢复。为了检验这个假设，两个问题将是 地址：1）在功能上进行电气或突触性能的变化 在组织学恢复后识别出肌脑神经元持续或出现 从炎症中：2）对神经源性推进运动活动的改变 完整的结肠持续或从炎症中恢复后出现？在 进行这些研究，我们将实施 技术，包括神经元的细胞内记录和标记， 逆行轴突跟踪，免疫组织化学和运动性测定。这些 结果将提高我们对神经免疫机制的理解 与炎症肠有关的整合和运动障碍 疾病和功能性肠病。