Age-induced decrease of glycoprotein Po and myelin basic protein gene expression in the rat sciatic nerve. Repair by steroid derivatives 1 This paper is dedicated to Prof. Béla Halasz, on the occasion of his 70th birthday. 1

Age-induced decrease of glycoprotein Po and myelin basic protein gene expression in the rat sciatic nerve. Repair by steroid derivatives 1 This paper is dedicated to Prof. Béla Halasz, on the occasion of his 70th birthday. 1
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DOI:
10.1016/s0306-4522(97)00628-3
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发表时间:
1998-04
期刊:
影响因子:
3.3
通讯作者:
R. Melcangi;Valerio Magnaghi;Ilaria T. Cavarretta;Luciano Martini;F. Piva
R. Melcangi;Valerio Magnaghi;Ilaria T. Cavarretta;Luciano Martini;F. Piva
中科院分区:
医学3区
文献类型:
--
作者:
R. Melcangi;Valerio Magnaghi;Ilaria T. Cavarretta;Luciano Martini;F. Piva

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这里报道的数据表明,在正常雄性大鼠的坐骨神经中,周围神经系统中髓鞘的主要成分的糖蛋白Po和髓鞘碱性蛋白的基因表达随着年龄的增长而显著降低。用二氢孕酮(孕酮的5α-还原衍生物)治疗一个月,能够部分恢复老年雄性大鼠坐骨神经中Po基因表达的下降,而不显著改变髓鞘碱性蛋白的基因表达。在新生儿许旺细胞(参与髓鞘合成的外周神经系统成分)的培养中,加入孕酮和二氢孕酮显著增加Po基因表达;二氢孕酮的3α还原代谢物四氢孕酮被证明更有效。这些数据表明,孕酮的作用与其转化为二氢孕酮,特别是转化为四氢孕酮有关,因为雪旺细胞具有5α-还原酶-3 α-羟基类固醇脱氢酶系统。这些数据提供了第一个证明,衰老降低了坐骨神经中外周髓鞘的两个主要成分的基因表达;他们还表明,这种现象可能会部分逆转孕酮衍生物,这可能会通过刺激Po基因表达的雪旺细胞。
The data here reported show that the gene expression of the glycoprotein Po and of the myelin basic protein, the major components of myelin in the peripheral nervous system, dramatically decreases with ageing in the sciatic nerve of normal male rats. A one-month treatment with dihydroprogesterone, the 5α-reduced derivative of progesterone, is able to partially restore the fall in Po gene expression occuring in the sciatic nerve of aged male rats, without significantly modifying the gene expression of the myelin basic protein. In cultures of neonatal Schwann cells (the peripheral nervous system elements involved in the synthesis of myelin), the addition of progesterone and of dihydroprogesterone significantly increases Po gene expression; the 3α-reduced metabolite of dihydroprogesterone, tetrahydroprogesterone proved to be even more effective. These data suggest that the effect of progesterone is linked to its conversion into dihydroprogesterone and especially into tetrahydroprogesterone, since Schwann cells possess the 5α-reductase-3α-hydroxysteroid dehydrogenase system. The data provide the first demonstration that ageing decreases the gene expression of two major components of the peripheral myelin in the sciatic nerve; they also show that this phenomenon may be partially reversed by progesterone derivatives, which might act by stimulating Po gene expression in the Schwann cells.