NEUROCHEMICAL SPINAL CIRCUITRY AND UTERINE INNERVATION

神经化学脊髓回路和子宫神经支配

• 批准号: 2902133
• 负责人: RAYMOND E PAPKA
• 金额: $ 14.49万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2902133
• 关键词: NEUROCHEMICAL; SPINAL; CIRCUITRY; UTERINE; INNERVATION

DESCRIPTION: (Adapted from applicant's abstract) The long-term goal of this research is to understand spinal cord and other CNS mechanisms for integration of uterine information and how these play a role in such pathologic conditions as autonomic dysreflexia and pregnancy-induced hypertension. The current proposal is designed to reveal spinal cord mechanisms for integration of uterine information and how these mechanisms relate to the altered physical and steroid hormone environment of pregnancy and parturition and the changing steroid hormone environment of the estrous cycle. Distinct subpopulations of spinal neurons innervate different pelvic organs (e.g., bladder versus colon). This specificity of neural organization led to the hypothesis: uterine-related neurons in the lumbosacral spinal cord provide the central mechanisms to integrate uterine information, these mechanisms involve estrogen-receptive neurons and process uterine information important in pregnancy and parturition and neuroendocrine reflexes. A specific role for estrogen in these pathways is hypothesized because estrogen modulates neurochemical systems in the CNS and influences sensitivity of primary afferent nerves. Consequently, the proposed studies are designed to address five specific aims: 1) determine if there are uterine-related neurons in the lumbosacral spinal cord, brainstem and hypothalamus and determine if these neurons have a special topography, 2) determine if there are estrogen receptor(ER)-containing neurons in the lumbosacral cord and brainstem, if uterine-related neurons contain ER, and if these neurons are altered with the changing hormonal milieu during pregnancy and parturition and during the estrous cycle, 3) identify neurotransmitters of intrinsic and descending projection inputs to uterine-related neurons and determine if their patterns are altered with the changing hormonal milieu during pregnancy and parturition and during the estrous cycle, 4) evaluate neurotransmitters of primary afferent input to uterine-related neurons and determine if their patterns are altered with the changing hormonal milieu during pregnancy and parturition and during the estrous cycle, and 5) determine if uterine-related lumbosacral spinal neurons respond to stimulation of uterine afferents, if some of these project to the hypothalamus and contain ERs. These studies will utilize transneuronal tract-tracing combined with immunohistochemistry, mechanical stimulus- induced activation of uterine-related spinal neurons and retrograde tracing. Animals used in these studies include pregnant and parturient rats, cycling rats and hormonally-manipulated rats. Health benefits will be derived from the results of this proposal. This information will increase our understanding of involvement of neural mechanisms in human pregnancy and parturition, hormonal influences on these central mechanisms and how the central mechanisms and pathways relate to neural- endocrine coordination of gestational events and such problems as preterm labor, pathologic conditions such as autonomic dysreflexia associated with spinal cord injury and pregnancy-induced hypertension.

描述：（改编自申请人的摘要）长期目标 这项研究旨在了解脊髓和其他中枢神经系统机制 子宫信息的整合以及它们如何在这样的过程中发挥作用 自主神经反射异常和妊娠引起的病理状况 高血压。 目前的提议旨在揭示脊髓 子宫信息整合机制以及这些机制如何 机制与改变的物理和类固醇激素有关 怀孕和分娩的环境以及类固醇的变化 动情周期的激素环境。 不同的亚群 脊髓神经元支配不同的盆腔器官（例如，膀胱与 冒号）。 神经组织的这种特殊性导致了以下假设： 腰骶脊髓中与子宫相关的神经元提供 整合子宫信息的中央机制，这些机制 涉及雌激素接受神经元并处理子宫信息 对怀孕和分娩以及神经内分泌反射很重要。 一个 推测雌激素在这些途径中的特定作用是因为 雌激素调节中枢神经系统的神经化学系统并影响 初级传入神经的敏感性。 因此，拟议的 研究旨在解决五个具体目标：1）确定是否 腰骶脊髓中有与子宫相关的神经元， 脑干和下丘脑，并确定这些神经元是否具有特殊的 地形图，2）确定是否含有雌激素受体（ER） 腰骶索和脑干中的神经元（如果与子宫相关） 神经元含有 ER，如果这些神经元随着变化而改变 怀孕、分娩和发情期间的荷尔蒙环境 循环，3）识别内在神经递质和下行神经递质 将输入投射到子宫相关神经元，并确定它们是否 模式会随着怀孕期间荷尔蒙环境的变化而改变 和分娩以及动情周期期间，4) 评估 子宫相关神经元初级传入输入的神经递质 并确定他们的模式是否随着荷尔蒙的变化而改变 怀孕和分娩期间以及发情周期期间的环境， 5) 确定子宫相关腰骶脊髓神经元是否有反应 刺激子宫传入神经，如果其中一些投射到子宫传入神经 下丘脑并含有 ER。 这些研究将利用跨神经元 纤维束追踪结合免疫组织化学、机械刺激 诱导子宫相关脊髓神经元的激活和逆行 追踪。 这些研究中使用的动物包括怀孕和产妇 大鼠、循环大鼠和激素调节大鼠。 健康益处将 源自该提案的结果。 该信息将 增加我们对人类神经机制参与的理解 怀孕和分娩，荷尔蒙对这些中枢的影响 机制以及中心机制和途径如何与神经相关 妊娠事件的内分泌协调和诸如此类的问题 早产、病理状况，例如自主神经反射异常 与脊髓损伤和妊娠高血压综合征有关。