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）：存在的运动障碍 在肠道炎症期间，反映了之间的显着相互作用 炎症介质和肠神经系统。的神经机制 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。第一个假设是炎症导致 内在初级传入神经元的兴奋性，导致失衡 在蠕动反射回路中。该假设将由 解决两个问题：1) 电学或突触特性 功能上鉴定的肌间神经元在实验性结肠炎期间发生变化？ 2) 是完整豚鼠结肠的神经源性推进运动活动 炎症期间改变？第二个假设是，变化 由炎症引起的蠕动反射回路持续跟随 组织病理学恢复。为了检验这个假设，有两个问题 解决：1）功能性改变电或突触特性 确定的肌间神经元持续存在或在组织学恢复后出现 炎症：2）改变神经源性推进运动活动 完整的结肠会持续存在还是在炎症恢复后出现？在 进行这些研究时，我们将实施综合组合 技术，包括神经元的细胞内记录和标记， 逆行轴突追踪、免疫组织化学和运动测定。这些 结果将增进我们对神经免疫机制的理解 与炎症性肠相关的整合和运动障碍 疾病和功能性肠道疾病。

项目成果

Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome.

溃疡性结肠炎和肠易激综合征中粘膜血清素含量的分子缺陷和血清素再摄取转运蛋白的减少。

• 发表时间: 2004-06
• 影响因子: 29.4
• 作者: Coates, Matthew D;Mahoney, Christine R;Linden, David R;Sampson, Joanna E;Chen, Jason;Blaszyk, Hagen;Crowell, Michael D;Sharkey, Keith A;Gershon, Michael D;Mawe, Gary M;Moses, Peter L
• 通讯作者: Moses, Peter L