Oligodendrocytes interactions with glial cells and neurons in demyelinating disease

Abstract

This review delves into the crosstalk network between oligodendrocytes and other glial cells in the context of demyelinating diseases. Oligodendrocytes, the myelin-forming cells in the central nervous system (CNS), are crucial for maintaining the function and integrity of axons and myelin sheaths. In demyelination pathologies, various factors hinder the normal differentiation of oligodendrocyte precursor cells, obstructing the myelin regeneration process, which is a primary barrier to therapeutic myelin repair. Emerging evidence highlights the critical role of glial cell interactions in CNS homeostasis and myelin regeneration, increasing interest in the treatment of demyelinating diseases. This article reviews the role of interactions between oligodendrocytes and other CNS glial cells in demyelinating and neurological diseases. Previous findings suggest that other CNS glial cells influence the survival and metabolic activity of oligodendrocytes through cell interactions, significantly affecting myelin formation and impacting demyelinating diseases characterized by myelin regeneration disorders. Targeted modulation of oligodendrocytes and their interactions with other cells at specific temporal stages may indicate a novel therapeutic direction for demyelinating diseases and offer fresh perspectives on the study of mechanisms and therapeutic approaches for related neurological conditions.

1. Introduction

Glial cells, including oligodendrocytes (OLGs), microglia, and astrocytes, are the most numerous cells in the central nervous system (CNS). Each type of glial cells has a distinct function and plays various roles in the CNS [1]. They work in conjunction with neurons to maintain the homeostasis of the CNS through intercellular interactions [2]. Glial cells also exert direct or indirect effects on other cells in the CNS [3–5]. Recent studies suggest that understanding the relationships among different cell types is essential for comprehending the pathogenesis of neurological diseases rather than focusing only on a single cell type [6–8]. Elucidating the regulatory network among different types of glial cells is therefore crucial for obtaining a comprehensive understanding of the occurrence and progression of neurological disease.

OLGs are myelin-forming cells in the CNS [9]. They originate from oligodendrocyte precursor cells (OPCs) and undergo differentiation [10]. The primary function of OLGs is to produce myelin and facilitate the conduction of action potentials [11–13]. Additionally, OLGs secrete neurotrophic factors, promote the survival and function of neurons and other glial cells, and help maintain the dynamic balance of myelin in the CNS alongside other glial cells. OLGs play a crucial role in the regeneration of myelin following injury [14]. In animal models of demyelinating disease, OLGs can regenerate myelin, but this regeneration process may be temporary or fail under pathological conditions [15]. Therefore, it is essential to systematically understand and study the dynamic process of OLGs during myelin injury and the body's subsequent response.

It is increasingly recognized that interactions between different types of glial cells play important roles in regulating the health of myelin, which is the protective covering that surrounds nerve fibers [16]. OLGs, the cells that produce myelin, are potential targets for disease treatment because they play a critical role in maintaining the health of myelin. Hence, the impact of other glial cells on myelination is predominantly achieved by regulating the activity of OLGs. For instance, astrocytes help regulate the amount of cholesterol in the brain, which can affect the survival of OLGs and support the regeneration of myelin. Astrocytes also provide different types of assistance for myelin health during active injury than they do during regeneration after damage has already occurred [17]. Microglia, another type of glial cell, are crucial for maintaining myelin health. They help refine the myelin sheath through phagocytosis during growth and development, which is essential for the normal development, proliferation, and maturation of OLGs. Under disease conditions, microglia are concentrated in lesion areas and can produce proteins that affect the development of OPCs [18]. As OLGs are highly susceptible to microglia-derived factors, the influence of microglia gathered in the lesion area on OLGs cannot be ignored. High levels of proliferation and activation of microglia occur mainly in the early stage of multiple sclerosis (MS), especially in the active part of demyelination. This is more likely to occur during the early stages before the onset of pathology rather than during the later recovery stage. These findings suggest that glial cell interactions are pivotal in the pathogenesis and potential treatment of demyelinating diseases.