Melcangi R C, Magnaghi V, Martini L
Department of Endocrinology, University of Milan, Italy.
Prog Neurobiol. 2000 Feb;60(3):291-308. doi: 10.1016/s0301-0082(99)00028-3.
The process of aging deeply influences morphological and functional parameters of the peripheral nerves. Interestingly, recent observations performed in our laboratory on the rat sciatic nerves have indicated that the deterioration of myelin occurring in the peripheral nerves during aging may be explained by the fall of the messenger levels of the major peripheral myelin proteins (glycoprotein Po, myelin basic protein and peripheral myelin protein 22). At least in the case of the Po, the low levels of its messengers and of the protein itself found in aged animals are increased by the treatment with a physiological progesterone derivative like dihydroprogesterone. It has also been found that in normal adult male rats the levels of the messengers for Po in the sciatic nerve are increased by progesterone, dihydroprogesterone and tetrahydroprogesterone; surprisingly, the gene expression of peripheral myelin protein 22 is stimulated only by tetrahydroprogesterone. These observations have been confirmed in parallel studies performed on Schwann cell cultures. Since tetrahydroprogesterone does not bind to the progesterone receptor but is a ligand for the GABAA receptor, the hypothesis has been put forward that part of the steroidal effects reported might occur not through the classical progesterone receptor, but rather via an interaction with the GABAA receptor. In other experiments it has been found that the gene expression of Po may be decreased by orchidectomy and restored by treatment with the androgen dihydrotestosterone. Altogether, these observations suggest the future use of physiological and/ or synthetic steroid hormones as a possible therapeutic approach for some pathological situations occurring in peripheral nerves during aging and demyelinating diseases.
衰老过程会深刻影响外周神经的形态和功能参数。有趣的是，我们实验室最近对大鼠坐骨神经进行的观察表明，衰老过程中外周神经中髓鞘的退化可能是由于主要外周髓鞘蛋白（糖蛋白Po、髓鞘碱性蛋白和外周髓鞘蛋白22）信使水平的下降所致。至少就Po而言，在老年动物中发现的其信使和蛋白本身的低水平可通过用二氢孕酮等生理性孕酮衍生物治疗而升高。还发现，在正常成年雄性大鼠中，坐骨神经中Po的信使水平会因孕酮、二氢孕酮和四氢孕酮而升高；令人惊讶的是，外周髓鞘蛋白22的基因表达仅受四氢孕酮刺激。这些观察结果在对雪旺细胞培养物进行的平行研究中得到了证实。由于四氢孕酮不与孕酮受体结合，而是GABAA受体的配体，因此有人提出，所报道的部分甾体效应可能不是通过经典的孕酮受体发生，而是通过与GABAA受体的相互作用发生。在其他实验中发现，Po的基因表达可通过去势降低，并通过用雄激素二氢睾酮治疗恢复。总之，这些观察结果表明，生理和/或合成甾体激素未来可能作为一种治疗方法，用于治疗衰老和脱髓鞘疾病期间外周神经出现的某些病理情况。
