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：失去膀胱控制有一个主要的不利因素， 对遭受各种创伤和疾病妇女和男子的影响 包括脊髓损伤、间质性膀胱炎、压力 失禁、多发性硬化、衰老和其他。 的病因 膀胱功能障碍对于这些组中的每一个都是不同的，但都是 神经性的 我的长期目标是提供关于神经控制的数据 可以用于开发药物的机制， 为这些人群恢复有用的膀胱功能。 实现这一 目标，有必要建立神经通路， 控制膀胱的神经递质，并测试它们的突触 连接因实验性损伤或疾病而改变。 这些数据可以用于开发药物， 恢复人类膀胱功能的途径。 虽然经常进行 不考虑性别，在过去的15年里， 多年来，在划定正常的 神经回路连接到膀胱 最近在骶骨的实验 猫的脊髓提供了新的数据， 膀胱控制机制的概念，这可能会改变未来 实验和临床的方法。 这些实验 表明（1）可能存在一种以上节前神经元 支配膀胱（目前的想法只包括一种类型） （2）膀胱节前神经元具有多种功能 脊髓（目前认为不包括中枢功能）。 他们 进一步表明（3）膀胱节前神经元可能属于 一组形态上不同的节前神经元， 独特的树枝状结构 当前的目标 实验将是为了测试这些假设，并确定是否性别 在这一层次的组织中发挥着重要作用。在这些 骶神经电生理特性 将检查支配猫膀胱的节前神经元 功能亚组的证据。 此外，膀胱 节前神经元将充满示踪剂神经生物素， 用光学显微镜检查它们的树突和轴突结构， 提供了亚群和中枢功能的形态学证据， 包括膀胱节前神经元的复发性抑制; 非膀胱节前神经元的相互抑制;和 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 脊髓内的突触作为进一步确认中央 功能，并作为识别神经递质的前体， 这些终扣。突触上的特定树突的膀胱节前 神经元将被检查，以提供关于中枢神经系统的信息。 对这些神经元的传入控制，并提供初步的 这些部位神经递质的信息 这些实验 对于准确理解膀胱反射是至关重要的 途径和实现膀胱控制的长期目标。