STEROID HORMONES AND NEURONAL REGENERATION

描述：研究人员已经确定了睾丸激素的作用 丙酸(TP)促进面部挤压伤后神经元再生 成年仓鼠的神经。据认为，睾丸素调节其 通过雄激素受体(AR)在男性中更为普遍的作用 并存在于这个特殊神经元的表面 子类型。此前，类固醇通过其作用机制的工作模型 增强周围神经再生已有研究进展。主 该项目的目标是测试该模型的特定方面，包括 特别关注再生反应的最初损伤阶段 以及雄激素受体在这些早期现象中的作用。这个 目的是检验以下4个假说。首先，研究表明，TP 面神经损伤同时给药改变早期应激 损伤FMN的反应。两个系列的实验，利用Northern 结合热休克蛋白70的印迹和免疫印迹程序 将使用cDNA探针和抗体来确定茶多酚对细胞的影响 损伤FMN的应激反应。第二，茶多酚对面部的影响 神经再生发生在FMN损伤的初期阶段。 响应，尽管之前的所有研究都使用TP管理 漫长的时间段。为了在早期了解TP是否有效，TP暴露将 限于面神经损伤后6-2小时和2 我们将进行一系列的分析。放射性同位素标记程序将是 用来确定有限的TP暴露对面部的影响 神经再生及与细胞骨架的原位杂交研究 将进行探测，以确定有限的TP暴露对 整个恢复期的细胞骨架反应模式。第三， 茶多酚促进面神经再生的性别差异 都是AR介导的。在3个系列的实验中，女性将优先获得TP 对面神经损伤，以上调AR基因的表达水平 以及茶多酚对面神经再生的影响，以及 将确定rRNA/细胞骨架基因的表达。第四，雌二醇 (E)通过AR促进种族神经再生。它已经被证明了 从面神经损伤时注射的E会导致雄激素- 比如再生速度的加快。两个系列的实验将是 搞定了。在存在抗雄激素的情况下，高剂量的E的作用， 氟他胺，以及高剂量和低剂量的E对再生速度的影响 要下定决心。还将进行AR结合分析，以确定E是否结合 到面神经核内的AR。

DESCRIPTION: The investigator has identified a role for testosterone propionate (TP) in enhancing neuronal regeneration of the crushed facial nerve in adult hamsters. It is thought that testosterone mediates its actions through androgen receptors (AR) that are more prevalent in males than in females and are present at the surface of this particular neuronal subtype. Previously, a working model of the mechanism by which steroids augment peripheral nerve regeneration has been developed. The main objective of this project is to test specific aspects of this model, with particular focus on the initial injury phases of the regenerative response and on the role of the androgen receptor in these early phenomena. The aims are to test the following 4 hypotheses. First, it was shown that TP administration coincident with facial nerve injury alters early stress responses of injured FMN. Two series of experiments, utilizing northern blot and immunoblot procedures in conjunction with heat shock protein 70 cDNA probes and antibodies will be used to determine the effect of TP on the stress response of injured FMN. Second, the effects of TP on facial nerve regeneration occur during the initial stages of the FMN injury response although all previous studies have used TP administration for lengthy time periods. To learn if TP can work early on, TP exposure will be limited to time periods of 6-2 hours after facial nerve injury and 2 series of analyses will be done. Radioisotopic labeling procedures will be used to determine the effects of limited Tp exposure on the rate of facial nerve regeneration, and in situ hybridization studies with cytoskeletal probes will be done to determine the effects of limited TP exposure on cytoskeletal response patterns throughout the recovery period. Third, the gender differences in the augmentation of facial nerve regeneration by TP are AR mediated. In 3 series of experiments, females will receive TP prior to facial nerve injury, in order to up-regulate levels of AR mRNA to those of males, and the effects of TP on facial nerve regeneration, and rRNA/cytoskeletal gene expression will be determined. Fourth, estradiol (E) acts via AR to augment racial nerve regeneration. It has been shown that E given from the time of facial nerve injury, results in an androgen- like acceleration of regeneration rates. Two series of experiments will be done. The effects of high doses of E in the presence of the anti-androgen, flutamide, and high versus low doses of E on the rate of regeneration will be determined. AR binding assays will also be done to determine if E binds to AR in the facial nucleus.