Gintonin Enhances Proliferation, Late Stage Differentiation, and Cell Survival From Endoplasmic Reticulum Stress of Oligodendrocyte Lineage Cells.

Mohammad Al Mijan,Sun-Hye Choi,Seung-Yeol Nah,So-Young Moon,Ji Young Kim,Hyun-Jeong Yang

doi:10.3389/fphar.2019.01211

Abstract

Although evidence on myelin diseases is steadily accumulating, effective preventive or therapeutic strategies against them have not been established so far. Ginseng is well known for its beneficial effects on health and diseases; however, detailed studies on ginseng’s effects on myelin-producing oligodendrocytes have not been performed yet. In this study, we investigated the function of gintonin—an active component of ginseng—on the proliferation, differentiation, and survival of oligodendrocyte lineage cells. We performed real-time percutaneous coronary intervention, Western blot, and immunocytochemistry on primary oligodendrocyte precursor cell cultures and in vitro myelinating co-cultures. Our results show that gintonin stimulates oligodendrocyte precursor cell proliferation. Gintonin’s effect was inhibited by Ki16425, an antagonist of lysophosphatidic acid 1/3 receptors. Interestingly, with regard to cell differentiation, gintonin facilitated late differentiation of oligodendrocyte development, but not early differentiation. Moreover, it showed protective effects on oligodendrocyte lineage cells against endoplasmic reticulum stress-induced cell death, potentially by modulating unfolded protein responses. Our results suggest that gintonin is a potential therapeutic candidate in the treatment of myelin diseases.

Highlights

Oligodendrocytes are glial cells that synthesize myelin, a material that wraps around axons and facilitates neuronal conduction in the central nervous system (Hughes and Appel, 2016)
To understand whether gintonin affects the initial step of oligodendrocyte development, we investigated oligodendrocyte precursor cells (OPCs) proliferation by gintonin treatment at different concentrations and at various time points in the proliferation medium that was devoid of differentiation-inducing hormones such as T3 and T4
There were no significant changes in the proliferation of oligodendrocyte lineage cells treated with gintonin dissolved in the differentiation medium containing T3 and T4 at the same time points (Supplementary Figures S1G–I)

Summary

Introduction

Oligodendrocytes are glial cells that synthesize myelin, a material that wraps around axons and facilitates neuronal conduction in the central nervous system (Hughes and Appel, 2016). Oligodendrocytes are derived from oligodendrocyte precursor cells (OPCs). Expression of transcription factors gradually changes along the developmental stages of oligodendrocyte lineage cells (Dwight E, 2016). During OPC development, certain transcription factors are expressed during the specific developmental stages. Hes, Id2, Id4, Sox, and Sox are expressed during the OPC stage and Myrf, Zfhx1b, Smad, and Nkx are expressed for the later stages (Cahoy et al, 2008). OPCs comprise approximately 5–8% of the glial cell population

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Discussion

Conclusion