SPINAL NEURONS CONTROLLING THE URINARY BLADDER

描述：失去对膀胱的控制有很大的危害 对遭受各种创伤和疾病的妇女和男子的影响 包括脊髓损伤、间质性膀胱炎、应激 大小便失禁、多发性硬化症、衰老等。致病原因 膀胱功能障碍在每一组中都是不同的，但都是 神经质。我的长期目标是提供有关神经控制的数据 可以用于药物开发的机制，可以 恢复这些人群有用的膀胱功能。要做到这一点 目标，有必要建立神经通路和 控制膀胱的神经递质和测试它们的突触 由于实验性损伤或疾病，连接会发生变化。 然后，这些数据可以用来开发可以作用于改变的药物 恢复人类膀胱功能的途径。虽然经常进行 不考虑性别，在过去的15年里，在动物模型中进行的实验 多年来，在描述正常情况方面取得了重大进展 通向膀胱的神经回路。最新的骶骨实验 猫的脊髓提供了挑战当前趋势的新数据 膀胱控制机制的概念以及可能改变未来的 该系统的实验和临床方法。这些实验 提示(1)节前神经元可能不止一种类型 支配膀胱(目前的想法只有一种) (2)膀胱节前神经元具有多种功能。 脊髓(当前思维不包括中枢功能)。他们 进一步提示(3)膀胱节前神经元可能属于 一组形态截然不同的节前神经元，具有 独特的树枝状结构。当前的直接目标是 实验将检验这些假设，并确定性别 在这一级别的组织中扮演着重要角色。在这些 实验：骶骨的电生理特性 将对支配猫膀胱的节前神经元进行检查 寻找功能亚群的证据。此外，膀胱 节前神经元将充满示踪剂神经生物素和 用光学显微镜观察它们的树突和轴突结构 提供亚群和中枢功能的形态证据， 包括对膀胱节前神经元的反复抑制； 对非膀胱节前神经元的相互抑制； 膀胱期对尿路括约肌的相互抑制 收缩。电子显微镜将用于检查轴突侧支 脊髓内的突触进一步证实中枢 功能，并作为鉴定神经递质的前驱 这些突触突触在节前膀胱的特定树突上 将对神经元进行检查，以提供有关中枢神经的信息 对这些神经元进行传入控制，并提供初步的 关于这些站点的神经递质的信息。这些实验 对于发展对膀胱反射的准确理解是必不可少的 这是一种新的治疗方法，有助于实现膀胱控制的长期目标。

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.