Developmental Plasticity of Micturition Reflexes

排尿反射的发育可塑性

• 批准号: 6895206
• 负责人: MARGARET Ann VIZZARD
• 金额: $ 25.76万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6895206
• 关键词: afferent nerve; confocal scanning microscopy; developmental neurobiology; fluorescent dye /probe; fos protein; immunocytochemistry; interneurons; laboratory rat; lumbosacral region; neural information processing; neural plasticity; neuroanatomy; newborn animals; parasympathetic nervous system; preganglionic fiber; radioimmunoassay; spinal reflex; suid alphaherpesvirus 1; urinary bladder; urination

DESCRIPTION (provided by applicant): The mechanisms involved in the storage and periodic elimination of urine exhibit marked changes during prenatal and postnatal development. In the young fetus, prior to maturation of the nervous system, urine is presumably eliminated from the urinary bladder by non-neural mechanisms. At later stages of development, micturition is regulated by spinal reflex pathways. As the central nervous system continues to mature during the postnatal period, reflex voiding is brought under voluntary control involving higher brain centers. In adults, injuries or diseases of the nervous system can lead to the reemergence of primitive functions that were prominent early in development but then were suppressed during neural maturation. Therefore, developmental studies of micturition reflex pathways are likely to provide key insights into the mechanisms underlying neurogenic disorders of urinary bladder function in adults. This research proposal will focus on alterations in spinal reflex voiding mechanisms that underlie the maturation of voiding function during the early postnatal period. Aim I). To determine the organization of urinary bladder interneurons and parasympathetic preganglionic neurons in the lumbosacral spinal cord. A combination of transneuronal tracing with pseudorabies virus (Bartha strain) and conventional retrograde dye mapping techniques (Fluorogold) will be utilized. Changes in connectivity between the various spinal elements will be assessed in postnatal rats prior to (P1, P7, P14) and following (P21, P28, P36) the emergence of the spinobulbospinal micturition reflex using design-based stereological techniques. Aim 2). To examine changes in central processing of afferent (A-s and/or C-fiber) information from the lower urinary tract of postnatal rats prior to and following the emergence of the spinobulbospinal micturition reflex. A combination of axonal tracing techniques and Fos protein expression will be utilized. These experiments will determine if A- and/or C-fiber bladder afferents are active during early postnatal development and how afferent information is processed by different neurons in different regions of the spinal cord. Aim 3). To examine the termination pattern, area occupied and morphology of perineal afferent nerve fibers and bulbospinal projections in close apposition to interneurons and/or preganglionic neurons in the lumbosacral spinal cord in postnatal rats prior to and following the emergence of the spinobulbosninal micturition reflex. These studies will determine if perineal afferent projections (Dil or WGA-HRP-labeled) and/or bulbospinal (CRF-IR) projections and varicosities are prominent in the lumbosacral spinal cord and which neuronal populations are in close apposition to afferent or bulbospinal efferent projections. Anatomical studies will be combined with immunoassay for CRF in the lumbosacral spinal cord.

描述(由申请人提供)：尿液储存和定期排出的机制在出生前和出生后的发育过程中表现出显著的变化。在年轻的胎儿中，在神经系统成熟之前，尿液可能通过非神经机制从膀胱中排出。在发育的后期，排尿受脊髓反射通路的调节。随着出生后中枢神经系统的不断成熟，反射性排尿受到更高级的大脑中枢的自愿控制。在成年人中，神经系统的损伤或疾病可能会导致原始功能的重新出现，这些功能在发育早期就很突出，但在神经成熟时被抑制。因此，对排尿反射通路的发育研究可能对成人膀胱功能神经源性障碍的机制提供关键的见解。这项研究建议将重点放在脊髓反射排尿机制的变化，这是出生后早期排尿功能成熟的基础。 目标i)。目的：确定腰骶段脊髓内膀胱中间神经元和副交感节前神经元的组织结构。将使用伪狂犬病病毒跨神经元追踪(Bartha株)和常规逆行染色绘制技术(荧光金)相结合的方法。使用基于设计的体视学技术，将在出生后大鼠(P1，P7，P14)和之后(P21，P28，P36)的脊髓球脊髓排尿反射出现之前和之后(P21，P28，P36)评估不同脊髓成分之间连通性的变化。 目标2)。目的：观察新生大鼠下尿路传入信息(A-S和/或C-纤维)在脊髓球脊髓排尿反射出现前后中枢加工的变化。将利用轴突追踪技术和Fos蛋白表达相结合的方法。这些实验将确定A和/或C纤维的膀胱传入在出生后早期是否活跃，以及脊髓不同区域的不同神经元如何处理传入信息。 目标3)。目的：观察脊髓球排尿反射出现前后，会阴传入神经纤维和球脊髓投射在腰骶段脊髓内与中间神经元和节前神经元紧密贴近的终末模式、面积和形态。这些研究将确定会传入投射(DIL或WGA-HRP标记)和/或球脊髓(CRF-IR)投射和静脉曲张是否突出，以及哪些神经元群体与传入或球脊髓传出投射密切相关。解剖学研究将与腰椎脊髓CRF的免疫分析相结合。