A putative functional role for oligodendrocytes in mood regulation

N Edgar,E Sibille

doi:10.1038/tp.2012.34

Abstract

Altered glial structure and function is implicated in several major mental illnesses and increasing evidence specifically links changes in oligodendrocytes with disrupted mood regulation. Low density and reduced expression of oligodendrocyte-specific gene transcripts in postmortem human subjects points toward decreased oligodendrocyte function in most of the major mental illnesses. Similar features are observed in rodent models of stress-induced depressive-like phenotypes, such as the unpredictable chronic mild stress and chronic corticosterone exposure, suggesting an effect downstream from stress. However, whether oligodendrocyte changes are a causal component of psychiatric phenotypes is not known. Traditional views that identify oligodendrocytes solely as nonfunctional support cells are being challenged, and recent studies suggest a more dynamic role for oligodendrocytes in neuronal functioning than previously considered, with the region adjacent to the node of Ranvier (i.e., paranode) considered a critical region of glial–neuronal interaction. Here, we briefly review the current knowledge regarding oligodendrocyte disruptions in psychiatric disorders and related animal models, with a focus on major depression. We then highlight several rodent studies, which suggest that alterations in oligodendrocyte structure and function can produce behavioral changes that are informative of mood regulatory mechanisms. Together, these studies suggest a model, whereby impaired oligodendrocyte and possibly paranode structure and function can impact neural circuitry, leading to downstream effects related to emotionality in rodents, and potentially to mood regulation in human psychiatric disorders.

Highlights

In the adult central nervous system (CNS), glial cells refer to a set of non-neuronal cells that provide support to neurons, and that include astrocytes, oligodendrocytes, ependymal cells and microglia
Myelin consists of lipids (70%) and a variety of proteins (30%), including myelin basic protein (MBP), proteolipid protein (PLP) and 20,30-cyclic nucleotide-30-phosphodiesterase (CNP), which together represent the major protein components of myelin.[9,10]
Mature oligodendrocytes are derived from oligodendrocyte precursor cells (OPC), which develop in specific ventricular zones, migrate to their final site in the brain, and differentiate

Summary

Introduction

In the adult central nervous system (CNS), glial cells refer to a set of non-neuronal cells that provide support to neurons, and that include astrocytes, oligodendrocytes, ependymal cells and microglia. Functional investigations of oligodendrocyte genes altered in schizophrenia point toward disruptions in cell cycle activity and axoglial interactions, at the node, thereby hinting at pathophysiological mechanisms.[31,32] evidence in bipolar disorder is more limited, reports indicate similar decreases in oligodendrocyte density,[26] oligodendrocyte-related genes primarily in the frontal cortex,[25,33,34] and white matter abnormalities[35] (reviewed in McIntosh et al.[36] and Mahon et al.[37]).

Results

Conclusion