A putative functional role for oligodendrocytes in mood regulation

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.

Figure 1

Schematic model of a putative stress-induced pathogenic process at the paranode and node of Ranvier. Evidence suggests that disruption of paranode molecule composition (e.g., stress or CNP1/CASPR ablation) can affect its structural integrity (Right panel: swelling (gray shading), lower junction delineation). This could lead to altered support of axonal function within the node of Ranvier, and suboptimal conduction of action potentials along the axon (dotted red line), leading to decreased integrity of information transfer, to or within, critical brain regions, such as the amygdala. In turn, the integration of this altered information (e.g., emotional stimuli) may propagate throughout the corticolimbic circuitry involved in mood regulation, ultimately resulting in abnormal integration of emotional salience, and affecting subsequent related behaviors.