Jones K J, Oblinger M M
Department of Physical Therapy, University of Illinois at Chicago 60612.
J Neurosci. 1994 Jun;14(6):3620-7. doi: 10.1523/JNEUROSCI.14-06-03620.1994.
We have previously demonstrated that systemic administration of testosterone increases the rate of axonal regeneration following facial nerve crush in adult male hamsters. In this investigation, the molecular mechanisms by which androgens may enhance axonal regeneration were examined. Specifically, the following question was addressed using Northern blot and in situ hybridization with three cytoskeletal cDNA probes complementary to beta II-, beta III-, and alpha 1-tubulin mRNA: does exogenous testosterone augment axotomy-induced changes in tubulin mRNA expression in hamster facial motoneurons (FMN)? Adult male hamsters were subjected to unilateral facial nerve severance, with the opposite side serving as an internal control. One-half of the animals were subcutaneously implanted with Silastic capsules containing crystalline testosterone propionate and the other half implanted with blank capsules. Postoperative survival times were 2 and 7 d. At 2 d after axotomy alone, no changes in levels of any of the three tubulin mRNAs were observed in the injured FMN. However, by 7 d after axotomy, significant increases in all three tubulin mRNAs were observed. This time course of axotomy-induced changes in tubulin gene expression is consistent with findings in other injured neuronal populations. Administration of testosterone at the time of injury had two major effects on the cytoskeletal response pattern in axotomized FMN. First, testosterone differentially regulated the set of tubulin mRNAs examined, in that beta II-tubulin mRNA levels were selectively altered by the steroid, whereas beta III- or alpha 1-tubulin mRNAs were not.(ABSTRACT TRUNCATED AT 250 WORDS)
我们之前已经证明,在成年雄性仓鼠面神经挤压后,全身性给予睾酮可提高轴突再生速率。在本研究中,我们检测了雄激素增强轴突再生的分子机制。具体而言,我们使用Northern印迹法以及与βII-、βIII-和α1-微管蛋白mRNA互补的三种细胞骨架cDNA探针进行原位杂交,探讨了以下问题:外源性睾酮是否会增强仓鼠面神经运动神经元(FMN)中轴突切断诱导的微管蛋白mRNA表达变化?成年雄性仓鼠接受单侧面神经切断,对侧作为内部对照。一半动物皮下植入含有结晶丙酸睾酮的硅橡胶胶囊,另一半植入空白胶囊。术后存活时间为2天和7天。仅在轴突切断后2天,未观察到损伤的FMN中三种微管蛋白mRNA水平有任何变化。然而,在轴突切断后7天,观察到所有三种微管蛋白mRNA均显著增加。轴突切断诱导的微管蛋白基因表达变化的这一动态过程与其他受损神经元群体的研究结果一致。损伤时给予睾酮对轴突切断的FMN中的细胞骨架反应模式有两个主要影响。首先,睾酮对所检测的微管蛋白mRNA有不同的调节作用,即该类固醇选择性地改变了βII-微管蛋白mRNA水平,而βIII-或αI-微管蛋白mRNA则未受影响。(摘要截短至250字)