COBRE: UNV MED SCH: P4: REMODELING OF NEUROMUSCULAR CONTROL IN GI SMOOTH MUSCLE

COBRE：UNV MED SCH：P4：胃肠道平滑肌神经肌肉控制的重塑

• 批准号: 7382019
• 负责人: NICK SPENCER
• 金额: $ 21.19万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7382019
• 关键词: COBRE; UNV; MED; SCH; P4

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The movement of luminal contents along the gastrointestinal (GI) tract is generated by contractions and relaxations of the tunica muscularis. These contractions propel luminal contents in an oral to aboral direction along the GI tract. When a partial luminal obstruction occurs, which impairs the normal flow of contents, the bowel ceases to function properly. One of the most pronounced changes that occur in response to bowel obstruction is the dramatic increase in the number and size of individual smooth muscle cells and a marked enlargement of enteric neurons. Despite the prevalence of hypertrophy in GI tissues and the well documented structural changes that occur, the mechanisms underlying this response to increased functional demands and the physiological changes that occur during this process are very poorly defined. This lack of understanding may in part be attributable to the failure to employ state of the art integrative technologies to examine this problem. The novel techniques described in this proposal will provide an unprecedented insight into the mechanisms underlying the pathophysiological changes that occur in response to colonic hypertrophy. These techniques will include patch clamp and intracellular microelectrode recordings, calcium imaging, immunohistochemistry, neurotransmitter release studies, single cell RT-PCR and a proteomics approach. We will determine which elements of the neuro-neuronal and neuromuscular transmission pathways are affected by colonic hypertrophy. The physiological changes that occur during hypertrophy will be examined using mutant mice which exhibit colonic hypertrophy and mice in which hypertrophy is induced by a partial obstruction of the colon. This study will also provide the first comprehensive analysis of the hypertrophic changes in the neuronal circuits and chemical coding of specific classes of enteric neurons. In addition, these studies will determine if smooth muscle displays plasticity and can revert to its original state following recovery from colonic hypertrophy.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。管腔内容物沿着胃肠道的运动是由肌层的收缩和舒张产生的。这些收缩沿着胃肠道从口腔到口腔方向推动管腔内容物。当发生部分管腔阻塞时，会损害内容物的正常流动，肠道就会停止正常运作。肠梗阻引起的最显着的变化之一是单个平滑肌细胞的数量和大小急剧增加以及肠神经元显着增大。尽管胃肠道组织肥大普遍存在，并且发生的结构变化有据可查，但这种对功能需求增加的反应的机制以及在此过程中发生的生理变化的机制尚不清楚。这种缺乏理解的部分原因可能是未能采用最先进的综合技术来研究这个问题。该提案中描述的新技术将为结肠肥大引起的病理生理变化的机制提供前所未有的见解。这些技术将包括膜片钳和细胞内微电极记录、钙成像、免疫组织化学、神经递质释放研究、单细胞 RT-PCR 和蛋白质组学方法。我们将确定神经神经元和神经肌肉传输途径的哪些元素受到结肠肥大的影响。将使用表现出结肠肥大的突变小鼠和通过部分结肠阻塞诱导肥大的小鼠来检查肥大期间发生的生理变化。这项研究还将首次对神经元回路的肥大变化和特定类别的肠神经元的化学编码进行全面分析。此外，这些研究将确定平滑肌是否表现出可塑性，并可以在结肠肥大恢复后恢复到原始状态。