Role of stress-related glucocorticoid changes in astrocyte-oligodendrocyte interactions that regulate myelin production and maintenance.

Abstract

Repeated activation of stress responses and elevated corticosteroids result in alterations of neuronal physiology and metabolism, and lead to disturbances of normal connectivity between neurons in various brain regions. In addition, stress responses are also associated with anomalies in the function of glial cells, particularly astrocytes and oligodendrocytes, which in turn may further contribute to the mechanisms of neuronal dysfunction. The actions of corticosteroids on astrocytes are very likely mediated by the presence of intracellular and cell membrane-bound CORT receptors. Although apparently less abundant than in astrocytes, activation of CORT receptors in oligodendrocytes also leads to structural changes that are reflected in myelin maintenance and plasticity. The close interactions between astrocytes and oligodendrocytes through extracellular matrix molecules, soluble factors and astrocyte-oligodendrocyte gap junctions very likely mediate part of the disturbances in myelin structure, leading to plastic myelin adaptations or pathological myelin disruptions that may significantly influence brain connectivity. Likewise, the intimate association of the tips of some astrocytes processes with a majority of nodes of Ranvier in the white matter suggest that stress and overexposure to corticosteroids may lead to remodeling of node of Ranvier and their specific extracellular milieu.