STEROID HORMONES AND NEURONAL REGENERATION

从性腺类固醇激素对大脑作用的研究来看， 普遍认为，这些药物对许多人具有神经营养作用 神经元存活和功能的方面。最近的临床和 实验证据表明，性腺可能具有治疗作用。 促进神经元再生。我们最近证明了 系统地给药雄激素丙酸睾丸酮(TP)，以 成年雄性仓鼠加速面瘫功能恢复 由面神经挤压所致。重要的是，面部运动神经元包含 雄激素受体。茶多酚是如何达到这种治疗效果的 为人所知。我们研究的长期目标是确定 TP促进面神经功能恢复的机制 损坏。为了实现这一目标，这项提案的具体目标将是 来检验以下4个假设。第一个要检验的假设是 茶多酚促进面神经损伤后面瘫的恢复 通过增加再生轴突和/或 缩短了萌芽形成的初始延迟。两个系列 实验，涉及轴向运输的放射性同位素标记 蛋白质，将被用来评估TP对轴突的影响 再生特性。需要检验的第二个假设是 茶多酚对周围神经功能恢复的促进作用 损伤是由雄激素受体介导的。两个系列的实验将是 用来确定TP对受损神经元的作用是否是雄激素 受体介导的。首先，雄激素受体将被阻断， 面神经挤压伤轴索切断及茶多酚对功能的影响 回收工作已确定。在第二个实验中，一群运动神经元 没有雄激素受体(脑神经VI)会受到挤压 神经切断及茶多酚对功能恢复的影响。这个 需要检验的第三个假设是TP加速了面部的恢复 面神经挤压后的瘫痪涉及核糖体的改变 面部运动神经元中RNA基因的表达。性腺激素的作用 大脑中的类固醇被认为是通过神经元的改变而产生的。 基因表达。核糖体RNA代表了一种丰富的、容易的 已知受轴突切断影响的可量化RNA物种 类固醇激素对靶神经元的作用。原位杂交法检测 基因组核糖体DNA探针将被用来确定是否显著 面部创伤后rRNA表达模式的改变 TP暴露后的神经元。需要检验的第四个假设是 茶多酚促进面神经挤压后面神经麻痹的恢复 涉及面部运动神经元内蛋白质合成的变化。 荷尔蒙对靶组织功能的调节通常被认为 通过蛋白质表达的选择性改变而发生。枢椎切断术 也已被证明选择性地影响蛋白质的合成 再生的神经元。放射性标记与二维凝胶 将进行电泳法以确定TP诱导的蛋白质变化 受损的面部神经元的合成。

From studies of gonadal steroid hormone action on the brain, it is generally established that these agents exert neurotrophic effects on many aspects of neuronal viability and functioning. Recent clinical and experimental evidence suggests that gonadal may have a therapeutic role in promoting neuronal regeneration. We have recently demonstrated that systematic administration of the androgen, testosterone propionate(TP), to adult male hamsters accelerates functional recovery from facial paralysis induced by facial nerve crush. Importantly, facial motoneurons contain androgen receptors. How TP accomplishes this therapeutic effect is not known. The long term objective of our research is to determine the mechanism underlying the TP-acceleration of recovery from facial nerve damage. Toward that objective, the specific aims of this proposal will be to test the following 4 hypotheses. The first hypothesis to be tested is that TP accelerates recovery from facial paralysis following facial nerve crush by increasing the growth rate of regenerating axons and/or shortening the initial delay of sprout formation. Two series of experiments, involving radioisotopic labeling of axonally transported proteins, will be employed to assess the effects of TP on axonal regenerative properties. The second hypothesis to be tested is that the TP-induced acceleration of functional recovery following peripheral nerve injury is androgen receptor-mediated. Two series of experiments will be done to determine if the action of TP on injured neurons is androgen receptor-mediated. In the first, androgen receptors will be blocked, the facial nerve crush axotomized, and the effects of TP on functional recovery determined. In the second, a population of motor neurons that do not have androgen receptors (cranial nerve VI) will be subjected to crush axotomy and the effects of TP on functional recovery determined. The third hypothesis to be tested is that TP-accelerated recovery from facial paralysis following facial nerve crush involves alterations in ribosomal RNA gene expression in facial motoneurons. The effects of gonadal steroids in the brain are thought to occur through alterations in neuronal gene expression. Ribosomal RNA represents an abundant, readily quantifiable RNA species that is known to be affected by axotomy and by steroid hormone action on target neurons. In situ hybridization with a genomic ribosomal DNA probe will be employed to determine if significant alterations in the pattern of rRNA expression occur in injured facial neurons following TP exposure. The fourth hypothesis to be tested is that TP-accelerated recovery from facial paralysis following facial nerve crush involves alterations in protein synthesis within faci: motoneurons. Hormonal regulation of target tissue functioning is generally considered to occur through selective changes in the expression of proteins. Axotomy also has been demonstrated to selectively affect protein synthesis in regenerating neurons. Radioactive labeling and two-dimensional gel electrophoresis will be done to identify TP-induced changes in protein synthesis in injured facial neurons.