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The Role of Astroglia in the Enteric Nervous System and Gut Function

星形胶质细胞在肠神经系统和肠道功能中的作用

基本信息

批准号：
8775246
负责人：
VLADIMIR PARPURA
金额：
$ 17.92万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-12-01 至 2017-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8775246
关键词：
Address Affect Animals Appearance Astrocytes Biological Assay Blood Vessels Brain Cells Chronic Colon Colonoscopy Connexin 43 Constipation Coupling Data Development Down-Regulation Duodenum Enteral Enteric Nervous System Eosine Yellowish Fiber Optics Gap Junctions Gastroenterology Gastrointestinal Diseases Gastrointestinal Transit Gastrointestinal tract structure Health Histology Histopathology Image Individual Inflammation Inflammatory Inflammatory Bowel Diseases Intervention Intestines Investigation Irritable Bowel Syndrome Knockout Mice Lead Light Link Maps Measurement Modeling Molecular Molecular Genetics Morphology Mucous Membrane Muscle Nature Necrotizing Enterocolitis Neonatal Neuraxis Neurobiology Neuroglia Pathology Patients Pattern Peristalsis Peroxidases Physiological Physiology Plasma Proteins Quality of life Reporting Role Survival Rate Testing Time Tissues Work cell motility chromophore clinical practice genetic approach ileum imaging modality improved in vivo innovation interest intestinal fatty acid binding protein jejunum microbial minimally invasive mouse model novel spatiotemporal translational medicine

项目摘要

DESCRIPTION (provided by applicant): The enteric nervous system (ENS) resides in the gut wall and controls physiology of the alimentary tract. The majority of the ENS is composed of enteric glial cells (EGCs), which have been linked to a wide range of gut pathologies, e.g., inflammatory bowel disease, necrotizing enterocolitis and "idiopathic" constipation. Our preliminary data point to a novel hypothesis that EGCs support normal gut function through their cell-cell connectivity established via connexin 43; the down regulation of Cx43 leads to inflammatory morphological changes and reduced motility of the gut. To test this hypothesis we will use an innovative molecular genetics approach integrated with histology, fiber-optic colonoscopy, GI transit tests in vivo, and an ex vivo imaging method of an isolated colon. This proposed investigation will gather valuable information on the novel role of Cx43 in the function of the gut and ENS. These findings will be of general interest to neurobiology. Additionally, the findings will be relevant to translational medicine, since they could open the door for the development of a cause-directed treatment for constipation and various inflammatory bowel diseases. These potential new opportunities for intervention could greatly improve clinical practice in gastroenterology by increasing the survival rate of neonatal patients suffering from necrotizing enterocolitis and substantially improve the quality of life and survival in the other ENS/EGC related gut pathologies.

描述(申请人提供)：肠道神经系统(ENS)驻留在肠壁，控制消化道的生理。大多数ENS由肠胶质细胞(EGCs)组成，这些细胞与多种肠道病理有关，如炎症性肠病、坏死性小肠结肠炎和特发性便秘。我们的初步数据指出了一种新的假设，即EGCs通过连接蛋白43建立的细胞-细胞连接来支持正常的肠道功能；Cx43的下调导致炎性形态变化和肠道动力降低。为了验证这一假设，我们将使用一种创新的分子遗传学方法，结合组织学、光纤结肠镜检查、体内胃肠道传输试验和体外分离结肠成像方法。这项拟议的研究将收集有关Cx43在肠道和ENS功能中的新角色的有价值的信息。这些发现将引起神经生物学的普遍兴趣。此外，这些发现将与转化医学相关，因为它们可能为便秘和各种炎症性肠道疾病的原因定向治疗的发展打开大门。这些潜在的新的干预机会可以通过提高新生儿坏死性小肠结肠炎患者的存活率来极大地改善胃肠病的临床实践，并显著改善与ENS/EGC相关的其他肠道病变的生活质量和生存。