STEROIDS AS TROPHIC FACTORS--AGING NEUROMUSCULAR SYSTEM

使用简单的神经肌肉系统，这项建议侧重于 雄激素对运动神经元数量维持的影响 在衰老中的形态和功能。这个系统由两个性爱系统组成 大鼠脊髓内的二形核、大鼠脊髓核 球海绵体肌(SNB)、背外侧核(DLN)和肌肉 它们所支配的会阴。虽然这些核存在于男性体内，但 它们的目标肌肉在女性身上减少或缺失。雄激素的作用是 在这个系统的发育和成年维持中的营养作用， 例如调节神经元的数量和树突的生长 运动神经元的发育、形态和维持 成年期的突触。建议进行的实验考察了 这些人的雄激素水平随着年龄的增长而下降 类固醇敏感运动神经元。它们有三个不同的特点 将对运动神经元种群进行检查：运动神经元数量、形态、 和功能。运动神经元数量将在一系列时间进行评估 与循环雄激素自然变化相对应的穴位 性二态和非二态类固醇敏感人群， 确定雄激素的下降是否反映在 运动神经元。通过维持雄激素水平或加速其 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 将检验与年龄相关的雄激素下降之间的因果关系。 运动神经元形态中结构可塑性的保留也将 要下定决心。最后，类固醇蓄积的功能方面和 兴奋性将根据年龄和荷尔蒙的变化进行评估。 条件。因为成熟哺乳动物体内的神经元是不可替代的 神经系统，了解控制死亡的因素 神经元的衰老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。

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.