Fargo Keith N, Sengelaub Dale R
Program in Neuroscience, Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana 47405, USA.
Dev Neurobiol. 2007 Jul;67(8):1094-106. doi: 10.1002/dneu.20454.
Motoneuron loss is a significant medical problem, capable of causing severe movement disorders or even death. We have been investigating the effects of motoneuron loss on surviving motoneurons in a lumbar motor nucleus, the spinal nucleus of the bulbocavernosus (SNB). SNB motoneurons undergo marked dendritic and somal atrophy following the experimentally induced death of other nearby SNB motoneurons. However, treatment with testosterone at the time of lesioning attenuates this atrophy. Because testosterone can be metabolized into the estrogen estradiol (as well as other physiologically active steroid hormones), it was unknown whether the protective effect of testosterone was an androgen effect, an estrogen effect, or both. In the present experiment, we used a retrogradely transported neurotoxin to kill the majority of SNB motoneurons on one side of the spinal cord only in adult male rats. Some animals were also treated with either testosterone, the androgen dihydrotestosterone (which cannot be converted into estradiol), or the estrogen estradiol. As seen previously, partial motoneuron loss led to reductions in soma area and in dendritic length and extent in surviving motoneurons. Testosterone and dihydrotestosterone attenuated these reductions, but estradiol had no protective effect. These results indicate that the neuroprotective effect of testosterone on the morphology of SNB motoneurons following partial motoneuron depletion is an androgen effect rather than an estrogen effect.
运动神经元损失是一个严重的医学问题，能够导致严重的运动障碍甚至死亡。我们一直在研究运动神经元损失对腰段运动核团——球海绵体肌脊髓核（SNB）中存活的运动神经元的影响。在实验诱导附近其他SNB运动神经元死亡后，SNB运动神经元会出现明显的树突和胞体萎缩。然而，在损伤时用睾酮治疗可减轻这种萎缩。由于睾酮可代谢为雌激素雌二醇（以及其他具有生理活性的类固醇激素），所以尚不清楚睾酮的保护作用是雄激素效应、雌激素效应，还是两者皆有。在本实验中，我们仅在成年雄性大鼠的脊髓一侧使用逆行运输的神经毒素杀死大部分SNB运动神经元。一些动物还接受了睾酮、雄激素双氢睾酮（不能转化为雌二醇）或雌激素雌二醇的治疗。如先前所见，部分运动神经元损失导致存活运动神经元的胞体面积、树突长度和范围减小。睾酮和双氢睾酮减轻了这些减小，但雌二醇没有保护作用。这些结果表明，在部分运动神经元耗竭后，睾酮对SNB运动神经元形态的神经保护作用是雄激素效应而非雌激素效应。
