Impacts of Spinal Cord Injury on Autonomic Neurons Responsible for Bladder Function

脊髓损伤对负责膀胱功能的自主神经元的影响

• 批准号: 10390870
• 负责人: Michael Leslie Gray
• 金额: $ 3.09万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10390870
• 关键词: Abnormal coordination; Acute; Address; Affect; Afferent Pathways; Age; Animals; Attenuated; Bladder; Bladder Control; Bladder Dysfunction; Calcium; Cells; Cessation of life; Choline O-Acetyltransferase; Chronic; Collection; Contracts; Devices; Dissection; Down-Regulation; Electrophysiology (science); Excision; Fire - disasters; Functional disorder; Ganglia; Gene Expression; General Population; Generations; Hyperreflexia; Incontinence; Injury; Ion Channel; Kidney; Knowledge; Lesion; Longevity; Measurement; Measures; Membrane; Messenger RNA; Micturition Reflex; Mus; Muscle; Nerve; Neurogenic Bladder; Neuromodulator Receptors; Neurons; Output; Pathway interactions; Pattern; Pelvis; Peripheral; Pharmacology; Phase; Physiological; Population; Potassium; Property; Quality of life; Quantitative Reverse Transcriptase PCR; Reflex action; Reporting; Research; Reverse Transcriptase Polymerase Chain Reaction; Severities; Signal Transduction; Skeletal Muscle; Spinal Cord; Spinal Cord transection injury; Spinal cord injury; Spinal cord injury patients; Stigmatization; Structure of parasympathetic ganglion; Time; Transcript; Transgenic Mice; Up-Regulation; Urethral sphincter; Urinary tract infection; Urogenital Diseases; Work; base; cell type; cholinergic; ganglion cell; improved; injured; mRNA Expression; mortality; mouse model; neuronal excitability; physically handicapped; promoter; protein degradation; public health relevance; receptor; receptor expression; spasticity; urologic; voltage clamp

Abstract (UNCHANGED FROM ORIGINAL APPLICATION) The circuit that controls the micturition reflex is composed of autonomic neurons that control smooth bladder muscle (Detrusor) and somatic (voluntary) neurons that control the skeletal muscle of the external urethral sphincter (EUS). After SCI, the coordination between these muscles is lost and they contract spontaneously. While something is known about how SCI alters the excitability of neuronal pathways that feed into the spinal cord (afferents) and how SCI alters the excitability of these muscles, relatively little is known how excitability of the neurons (autonomic bladder-innervating neurons) contained in a collection of neurons called the major pelvic ganglia (MPG) is altered. The primary aim of this proposal is to characterize how the excitability of these neurons changes after acute (3 days post injury) and chronic (28 days post injury) SCI. Mouse models of SCI will be used to determine how injury alters the ability of neurons to fire based on their intrinsic properties (as opposed to their input from other neurons). Underlying mechanisms for altered output will be investigated using voltage clamp and pharmacological dissection of ionic currents to measure changes in underlying membrane conductance. To determine whether underlying changes in membrane conductance are the result of alterations in channel expression, single-cell quantitative RT-PCR (qRT-PCR) will be used to measure transcript numbers from MPG neurons in injured and intact animals. The proposed work will greatly improve the basic understanding of bladder reflex circuitry by providing a much needed extension of the characterization of the physiological properties and underlying ionic mechanisms of MPG neuron function. In addition, these studies represent one of the first analyses of plasticity at the MPG as a result of SCI, with implications for the successful comprehensive treatment of neurogenic bladder dysfunction.

摘要（与原始应用没有变化） 控制排尿反射的电路由控制光滑膀胱的自主神经元组成 控制外部尿道骨骼肌 括约肌（EUS）。 SCI之后，这些肌肉之间的协调损失了，它们会自发收缩。 虽然关于SCI如何改变了进食脊柱的神经元途径的兴奋性的了解 电线（传入）以及科学如何改变这些肌肉的兴奋性，相对较少知道兴奋性如何 神经元中包含的神经元（自主膀胱发射神经元）的神经元中的神经元中的神经元中包含的神经元中包含 骨盆神经节（MPG）改变了。该提案的主要目的是表征如何兴奋 这些神经元在急性后（受伤后3天）和慢性（受伤后28天）科学变化。鼠标模型 SCI将用于确定损伤如何根据其内在特性来改变神经元的发射能力 （与其他神经元的输入相反）。将研究改变输出的基本机制 使用离子电流的电压夹和药理学解剖来测量底层的变化 膜电导。确定膜电导的潜在变化是否是 通道表达的改变，单细胞定量RT-PCR（QRT-PCR）将用于测量 受伤和完整动物中MPG神经元的转录数。拟议的工作将大大改善 通过提供急需的扩展，对膀胱反射电路的基本理解 MPG神经元功能的生理特性和基本离子机制的表征。在 此外，这些研究代表了由于SCI而在MPG处的最早可塑性分析之一，并与 对神经源性膀胱功能障碍的成功综合治疗的影响。