Ultrastructural Characterization of Human Oligodendrocytes and Their Progenitor Cells by Pre-embedding Immunogold.

María J Ulloa-Navas,Josée M García-Verdugo,Ana Saurí-Tamarit,Raquel Morales-Gallel,Pedro Pérez-Borredá,Vicente Herranz-Pérez,Antonio J Gutiérrez-Martín,Patricia García-Tárraga

doi:10.3389/fnana.2021.696376

Abstract

Oligodendrocytes are the myelinating cells of the central nervous system. They provide trophic, metabolic, and structural support to neurons. In several pathologies such as multiple sclerosis (MS), these cells are severely affected and fail to remyelinate, thereby leading to neuronal death. The gold standard for studying remyelination is the g-ratio, which is measured by means of transmission electron microscopy (TEM). Therefore, studying the fine structure of the oligodendrocyte population in the human brain at different stages through TEM is a key feature in this field of study. Here we study the ultrastructure of oligodendrocytes, its progenitors, and myelin in 10 samples of human white matter using nine different markers of the oligodendrocyte lineage (NG2, PDGFRα, A2B5, Sox10, Olig2, BCAS1, APC-(CC1), MAG, and MBP). Our findings show that human oligodendrocytes constitute a very heterogeneous population within the human white matter and that its stages of differentiation present characteristic features that can be used to identify them by TEM. This study sheds light on how these cells interact with other cells within the human brain and clarify their fine characteristics from other glial cell types.

Highlights

Oligodendrocytes are glial cells whose main function is myelination
Our results suggest that oligodendrocytes present three marked ultrastructural stages (Figure 1A): oligodendrocyte precursor cells (OPCs) labeled for NG2, A2B5 and PDGFRα; premyelinating oligodendrocytes (pre-OLs) labeled for BCAS1/NABC1, Sox10 and Olig2; and myelinating oligodendrocytes (m-OLs) labeled with APC-(CC1) and Olig2
Our results suggest that oligodendrocytes in the human white matter display three distinctive morphologies and can be labeled with distinctive molecular markers (Figure 1A)

Summary

Introduction

Oligodendrocytes are glial cells whose main function is myelination. Oligodendrocytes perform other supportive activities such as glucose metabolism (Amaral et al, 2016; Saab et al, 2016), calcium influx/efflux towards the axon to impede. After numerous studies in animal models, evidence suggests that in the postnatal brain oligodendrocytes arise from NG2/PDGFRa/Olig2-positive progenitors in different regions of the brain and spinal cord (Rivers et al, 2008; Zhu et al, 2008; Kang et al, 2010; Sánchez-González et al, 2020). The processes of oligodendrocyte replacement, maturation, and myelin regeneration play a critical role in the adult brain, where remodeling and plasticity are a constant phenomenon. When there is an insult in the brain, especially in the white matter such as in MS, NG2+-cells are recruited towards the lesions, and studies demonstrate their presence in MS plaques (Wilson et al, 2006)

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