17β-Estradiol Promotes Schwann Cell Proliferation and Differentiation, Accelerating Early Remyelination in a Mouse Peripheral Nerve Injury Model.

Yan Chen,Wenming Xu,Meng Cheng,Wenjuan Li,Ying Hu,Wenjie Guo,Liangzhi Xu

doi:10.1155/2016/7891202

Abstract

Estrogen induces oligodendrocyte remyelination in response to demyelination in the central nervous system. Our objective was to determine the effects of 17β-estradiol (E2) on Schwann cell function and peripheral nerve remyelination after injury. Adult male C57BL/6J mice were used to prepare the sciatic nerve transection injury model and were randomly categorized into control and E2 groups. To study myelination in vitro, dorsal root ganglion (DRG) explant culture was prepared using 13.5-day-old mouse embryos. Primary Schwann cells were isolated from the sciatic nerves of 1- to 3-day-old Sprague–Dawley rats. Immunostaining for myelin basic protein (MBP) expression and toluidine blue staining for myelin sheaths demonstrated that E2 treatment accelerates early remyelination in the “nerve bridge” region between the proximal and distal stumps of the transection injury site in the mouse sciatic nerve. The 5-bromo-2′-deoxyuridine incorporation assay revealed that E2 promotes Schwann cell proliferation in the bridge region and in the primary culture, which is blocked using AKT inhibitor MK2206. The in vitro myelination in the DRG explant culture determined showed that the MBP expression in the E2-treated group is higher than that in the control group. These results show that E2 promotes Schwann cell proliferation and myelination depending on AKT activation.

Highlights

Remyelination is an important aspect of nerve regeneration
60 30 d myelin sheath in the bridge site was found, and newly generated axons seldom underwent degeneration (Figure S1(C)), unlike the distal stump, wherein many degenerated axons and myelin sheaths were found via toluidine blue staining of semithin tissue slice (Figure S1(C))
In the longitudinal section slices of injured sciatic nerves, minimal expression of myelin basic protein (MBP) was found in the bridge site of control sciatic nerves, whereas sporadic signals of MBP expression were visible in the bridge site of E2-treated mice 10 days after injury (Figure 1(b))

Summary

Introduction

Remyelination is an important aspect of nerve regeneration. Sciatic nerve crush injury model is often used to study peripheral nerve remyelination because the crushed nerve always fully restores structure and function, despite seldom undergoing “abnormal fix” after injury [1, 2]. Developmental peripheral nerve myelination depends on extensive Schwann cell precursor proliferation [6,7,8],while remyelination in the distal stump of the crushed nerve seems to be independent of the proliferation of Schwann cell precursors generated during. Wallerian degeneration, but it rather relies on the existence of the original nonproliferating Schwann cells [9]. Remyelination in the “nerve bridge” may be difficult to attribute to the originally existing Schwann cells because the site is entirely

Objectives

Methods

Results