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

• 批准号: 8619205
• 负责人: VLADIMIR PARPURA
• 金额: $ 22.05万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8619205
• 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; ileum; imaging modality; improved; in vivo; innovation; interest; intestinal fatty acid binding protein; jejunum; microbial; minimally invasive; mouse model; novel; public health relevance; spatiotemporal; translational medicine

Abstract 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.

摘要 肠神经系统（ENS）位于肠壁中并控制消化道的生理学。的 大多数ENS由肠神经胶质细胞（EGCs）组成，EGCs与广泛的肠神经系统相关。 病理，例如，炎症性肠病、坏死性小肠结肠炎和“特发性”便秘。我们 初步的数据指出了一个新的假设，即EGCs通过它们的细胞间作用支持正常的肠道功能。 通过连接蛋白43建立连接; Cx43的下调导致炎性形态学改变。 肠道的变化和减少的运动。为了验证这一假设，我们将使用一种创新的分子遗传学， 结合组织学、光纤结肠镜检查、体内GI运输试验和体外成像的方法 分离结肠的方法。这项拟议中的调查将收集有关新作用的宝贵信息， Cx43在肠道和ENS功能中的作用。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有关，因为它们可以为人类的发展打开大门。 开发针对便秘和各种炎症性肠病的病因治疗。这些 潜在的新的干预机会可以大大改善胃肠病学的临床实践， 提高患有坏死性小肠结肠炎的新生儿患者的存活率， 改善其他ENS/EGC相关肠道病变的生活质量和生存率。