SPINAL NEURONS CONTROLLING THE URINARY BLADDER

控制膀胱的脊髓神经元

• 批准号: 2150250
• 负责人: CHARLES A MORGAN
• 金额: $ 12.34万
• 依托单位: EASTERN VIRGINIA MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2150250
• 关键词: cats; disease /disorder model; electron microscopy; gender difference; innervation; neuroanatomy; neurogenic urinary bladder disorder; neuromuscular function; neurophysiology; neurotransmitters; spinal nerves

DESCRIPTION: Loss of urinary bladder control has a major detrimental impact upon women and men suffering from a variety of trauma and disease including spinal cord injury, interstitial cystitis, stress incontinence, multiple sclerosis, aging, and others. The etiologies of bladder dysfunction are different for each of these groups, but all are neurogenic. My long term goal is to provide data on neural control mechanisms that can be used in the development of drugs which can restore useful bladder function to these populations. To attain this goal, it is necessary to establish the neural pathways and neurotransmitters controlling the bladder and to test how their synaptic connections are altered as a result of experimental injury or disease. These data can then be used to develop drugs that can act on altered pathways to restore bladder function in humans. Though often conducted without regard to gender, experiments in animal models over the past 15 years have made significant progress toward delineating the normal neural circuitry to the bladder. Recent experiments in the sacral spinal cord of the cat have provided new data which challenge current concepts of bladder control mechanisms and which may alter future experimental and clinical approaches to this system. These experiments indicate (1) there may be more than one type of preganglionic neuron innervating the urinary bladder (current thinking includes only one type) and (2) bladder preganglionic neurons have multiple functions within the spinal cord (current thinking includes no central function). They further indicate (3) that bladder preganglionic neurons may belong to a morphologically distinct group of preganglionic neurons that have a unique dendritic structure. The immediate goals of the current experiments will be to test these hypotheses and to determine if gender plays a significant role at this level of organization.In these experiments, the electrophysiological characteristics of sacral preganglionic neurons innervating the bladder in the cat will be examined for evidence of functional subgroups. Additionally, bladder preganglionic neurons will be filled with the tracer neurobiotin and their dendritic and axonal structure examined with light microscopy to provide morphological evidence of subgroups and of central functions, including recurrent inhibition of bladder preganglionic neurons; reciprocal inhibition of non-bladder preganglionic neurons; and reciprocal inhibition of the urethral sphincter muscles during bladder contraction.Electron microscopy will be used to examine axon collateral synapses within the spinal cord as further confirmation of central functions and as a precursor to identification of neurotransmitters in these boutons.Synapses upon specific dendrites of bladder preganglionic neurons will be examined to provide information regarding the central afferent controls made upon these neurons and to provide preliminary information on the neurotransmitters at these sites. These experiments are essential to developing an accurate understanding of bladder reflex pathways and toward achieving the long term goals of bladder control.

描述：膀胱控制损失具有严重的有害 对患有各种创伤和疾病的男性和男性的影响 包括脊髓损伤，间质性膀胱炎，压力 尿失禁，多发性硬化症，衰老等。 病因 膀胱功能障碍在这些组中有不同，但所有这些都是 神经源。 我的长期目标是提供有关神经控制的数据 可以用于开发药物的机制 恢复这些人群中有用的膀胱功能。 实现这一点 目标，有必要建立神经途径和 控制膀胱的神经递质并测试其突触 由于实验损伤或疾病而改变了连接。 然后可以使用这些数据来开发可以对变化作用的药物 恢复人类膀胱功能的途径。 虽然经常进行 不考虑性别，过去15个动物模型的实验 多年在划定正常状态方面取得了重大进展 神经回路向膀胱。 萨克里的最新实验 猫的脊髓提供了挑战当前的新数据 膀胱控制机制的概念，可能会改变未来 该系统的实验和临床方法。 这些实验 表明（1）可能有多种类型的前神经元 支配膀胱（当前的思维仅包括一种） （2）膀胱前神经元在 脊髓（当前思维不包括中心功能）。 他们 进一步表明（3）膀胱前神经元可能属于 具有形态上不同的gagionic神经元的群体，具有 独特的树突结构。 当前的直接目标 实验将是检验这些假设并确定性别是否 在这一级别的组织中起着重要的作用。 实验，骨的电生理特征 将检查猫中膀胱的神经gangionic神经元将被检查 用于功能亚组的证据。 另外，膀胱 前神经神经元将填充示踪剂神经蛋白和 它们的树突状结构和轴突结构用光学显微镜检查到 提供亚组和中心功能的形态学证据， 包括复发膀胱前神经元的抑制作用； 非叶片前神经元的相互抑制；和 膀胱期间尿道括约肌的相互抑制 收缩。电子显微镜将用于检查轴突侧支 脊髓内的突触，作为中央的进一步确认 功能和作为鉴定神经递质的先驱 这些胸部。在膀胱前的特定树突上的类似物 将检查神经元以提供有关中心的信息 对这些神经元的传入控制并提供初步 有关这些站点的神经递质的信息。 这些实验 对于对膀胱反射的准确理解至关重要 途径并实现膀胱控制的长期目标。