Neuroactive steroids stimulate peripheral myelination: a new therapeutical possibility for aging-associated degenerations of peripheral nerves

Abstract

In peripheral nerves, two important myelin proteins [i.e., glycoprotein Po (Po), and peripheral myelin protein 22 (PMP22)] play an important role for the maintenance of the multilamellar structure of PNS (peripheral nervous system) myelin. Modification in their synthesis occurs during the aging process, with a corresponding influence on myelin structure. Loss of myelinated fibers and alterations in their myelin structure and morphology are present in aged peripheral nerves. In adult male rats and in Schwann cell cultures, neuroactive steroids [e.g., progesterone (P), dihydroprogesterone (DHP), tetrahydroprogesterone, (THP), testosterone (T), dihydrotestosterone (DHT), and 5alpha-androstan-3alpha,17beta-diol (3alpha-diol)] stimulate the expression of Po and PMP22. Data here presented indicate that some neuroactive steroids may represent useful therapeutic approaches to maintain peripheral nerve integrity in aged animals. We demonstrate that, in sciatic nerve of aged rats, P and DHP stimulate expression of Po while THP stimulates that of PMP22. Consistent with these observations, P, DHP and THP also affect morphological parameters of sciatic nerve of aged rats. In particular, they increase the number of myelinated fibers of small caliber, reduce the frequency of myelin abnormalities and increase g-ratio of small myelinated fibers. Moreover, P treatment also reduces the frequency of myelinated fibers with irregular shapes. In contrast, neither T nor DHT or 3alpha-diol significantly affect expression of Po and PMP22 and any of the morphological parameters examined. (Financial support: QLK6-CT-2000–00179).