STEROIDS AS TROPHIC FACTORS--AGING NEUROMUSCULAR SYSTEM

类固醇作为营养因子--老化神经肌肉系统

• 批准号: 3121151
• 负责人: DALE R SENGELAUB
• 金额: $ 12.15万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3121151
• 关键词: aging; androgens; autoradiography; biological models; cell parasexuality; central nervous system; dendrites; electrophysiology; hormone regulation /control mechanism; innervation; laboratory rat; male; motor neurons; muscle; neural plasticity; neuroanatomy; neurogenesis; neuromuscular system; neurophysiology; spinal cord; synapses

Using a simple neuromuscular system, this proposal focuses on the influence of androgens in the maintenance of motoneuron number, morphology, and function in aging. This system consists of two sexually dimorphic nuclei in the rat spinal cord, the spinal nucleus of the bulbocavernosus (SNB) and the dorsolateral nucleus (DLN) and the muscles of the perineum they innervate. While present in males these nuclei and their target muscles are reduced or absent in females. Androgens serve a trophic function in the development and adult maintenance of this system, for example regulating neuron number and dendritic growth during development, and maintaining motoneuron morphology and synaptology in adulthood. The experiments proposed examine the effect of the declines in androgen levels that occur with advancing age on these steroid-sensitive motoneurons. Three different features of these motoneuron populations will be examined: motoneuron number, morphology, and function. Motoneuron number will be assessed at a series of time points corresponding to the natural changes in circulating androgen in both sexually dimorphic and nondimorphic steroid-sensitive populations, to determine whether declines in androgen are reflected in the loss of motoneurons. By maintaining androgen levels or accelerating their decline, the influence of androgens on motoneuron survival will be directly assessed. The normal time course of regressive changes and the causal relation with age-related declines in androgens will be tested. The retention of structural plasticity in motoneuron morphology will also be determined. Finally, functional aspects of steroid accumulation and excitability will be assessed with regard to changes with age and hormonal condition. Because neurons can not be replaced in mature mammalian nervous systems, understanding the factors which control the death of neurons in aging is critical for our understanding of the aging process and age-related declines in neurobehavioral function.

该提案使用简单的神经肌肉系统，重点关注 雄激素对维持运动神经元数量的影响， 衰老过程中的形态和功能。 该系统由两部分组成： 大鼠脊髓中的二形核，即脊髓核 球海绵体肌 (SNB) 和背外侧核 (DLN) 以及肌肉 它们支配会阴。 虽然存在于男性体内，但这些细胞核和 女性的目标肌肉减少或缺失。 雄激素的作用是 该系统的发育和成年维持中的营养功能， 例如调节神经元数量和树突生长 发育，并维持运动神经元形态和 成年期的突触学。 提出的实验检验了以下效果 随着年龄的增长，雄激素水平下降 类固醇敏感的运动神经元。 这些的三个不同的特点 将检查运动神经元群体：运动神经元数量、形态、 和功能。 将在一系列时间评估运动神经元数量 对应于循环雄激素自然变化的点 性二态性和非二态性类固醇敏感人群 确定雄激素的下降是否反映在雄激素的丧失中 运动神经元。 通过维持雄激素水平或加速雄激素水平 下降，雄激素对运动神经元存活的影响将是 直接评估。 回归变化的正常时间进程和 将测试与年龄相关的雄激素下降的因果关系。 运动神经元形态结构可塑性的保留也将 被确定。 最后，类固醇积累的功能方面和 将根据年龄和荷尔蒙的变化来评估兴奋性 健康）状况。 因为成熟哺乳动物的神经元无法被替换 神经系统，了解控制死亡的因素 衰老中的神经元对于我们理解衰老过程至关重要 以及与年龄相关的神经行为功能下降。