Afferent signaling in voiding reflex maturation

排尿反射成熟中的传入信号传导

• 批准号: 6849313
• 负责人: HSI-YANG WU
• 金额: $ 12.56万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-15 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6849313
• 关键词: SDS polyacrylamide gel electrophoresis; afferent nerve; autonomic reflex; biological signal transduction; calcium; capsaicin; corticotropin releasing factor; developmental neurobiology; laboratory rat; neurophysiology; pediatrics; polymerase chain reaction; smooth muscle; spinal cord injury; urinary bladder; urinary bladder epithelium; urination; urology

DESCRIPTION (provided by applicant): Improving our current therapies for pediatric voiding disorders requires an understanding of the neural events that underlie the maturation of voiding. Working with Dr. W.C. deGroat would assist me in becoming an independent investigator by providing a solid understanding of the neurophysiological approaches used in studying voiding dysfunction. The neonatal rat provides a model of bladder reflex maturation. Between birth and 3 weeks of life, emptying switches from dependence on maternal stimulation of the pudendal nerve to a centrally organized bladder reflex, and the spontaneous activity of the bladder changes from an organized pattern to a chaotic one. Two related hypotheses are proposed: 1. Maturation of central neural control of voiding is influenced by afferent input from the lower urinary tract. 2. The emergence of the mature storage function of bladder smooth muscle is regulated by autonomic nerve activity originating in the central nervous system. Two Specific Aims are proposed: 1. Determine if alteration of afferent input from the bladder changes maturation of voiding reflexes. 2. Determine if alteration of afferent input, with subsequent changes in the central nervous system, alters maturation of bladder smooth muscle. The timing of voiding reflex changes will be studied in early maternal separation, pudendal nerve transection, and neonatal capsaicin treatment. Early elimination of primitive reflexes and early onset of mature reflexes are anticipated. These preparations and early spinal cord injury will be used to study the maturation of bladder smooth muscle. The pattern of spontaneous bladder activity will be determined using in-vitro optical imaging of calcium and voltage signals. Changes in the site of origination and direction of propagation of spontaneous activity will help determine the relative importance of brain, spinal cord, and peripheral nervous system input on bladder maturation. The long-term goals of this study are to develop new, developmentally appropriate therapies for pediatric voiding dysfunction, and to determine whether bladder overactivity has a developmental origin.

描述（由申请人提供）： 改善我们目前对小儿缺乏疾病的疗法需要了解构成无效化成熟的神经事件。与W.C.博士合作Degroat将通过对用于研究空隙功能障碍的神经生理方法有深入的了解，帮助我成为独立研究者。新生大鼠提供了膀胱反射成熟的模型。在生命的出生和3周之间，排空从对孕产妇刺激的刺激到中央有组织的膀胱反射的转换，膀胱的自发活性从有组织的模式变为混乱。提出了两个相关的假设： 1。排序中心神经控制的成熟受到下尿路的传入输入的影响。 2。膀胱平滑肌的成熟存储功能的出现受到中枢神经系统中的自主神经活动的调节。 提出了两个具体目标： 1。确定膀胱传入输入的变化是否会改变无效反射的成熟。 2。确定传入输入的改变，随后中枢神经系统的变化，会改变膀胱平滑肌的成熟。 在早期的母体分离，底端神经横向和新生儿辣椒素治疗中，将研究无效反射变化的时间。预计会尽早消除原始反射和早期成熟反射。这些制剂和早期脊髓损伤将用于研究膀胱平滑肌的成熟。自发膀胱活性的模式将使用钙和电压信号的体外光学成像确定。自发活动的起源部位和传播方向的变化将有助于确定大脑，脊髓和周围神经系统对膀胱成熟的相对重要性。这项研究的长期目标是开发新的，发育的新疗法，用于儿科缺失功能障碍，并确定膀胱过度活动是否具有发育起源。