Astrocytes as Context for the Involvement of Myelin and Nodes of Ranvier in the Pathophysiology of Depression and Stress-Related Disorders

Astrocytes, despite some shared features as glial cells supporting neuronal function in gray and white matter, participate and adapt their morphology and neurochemistry in a plethora of distinct regulatory tasks in specific neural environments. In the white matter, a large proportion of the processes branching from the astrocytes’ cell bodies establish contacts with oligodendrocytes and the myelin they form, while the tips of many astrocyte branches closely associate with nodes of Ranvier. Stability of myelin has been shown to greatly depend on astrocyte-to-oligodendrocyte communication, while the integrity of action potentials that regenerate at nodes of Ranvier has been shown to depend on extracellular matrix components heavily contributed by astrocytes. Several lines of evidence are starting to show that in human subjects with affective disorders and in animal models of chronic stress there are significant changes in myelin components, white matter astrocytes and nodes of Ranvier that have direct relevance to connectivity alterations in those disorders. Some of these changes involve the expression of connexins supporting astrocyte-to-oligodendrocyte gap junctions, extracellular matrix components produced by astrocytes around nodes of Ranvier, specific types of astrocyte glutamate transporters, and neurotrophic factors secreted by astrocytes that are involved in the development and plasticity of myelin. Future studies should further examine the mechanisms responsible for those changes in white matter astrocytes, their putative contribution to pathological connectivity in affective disorders, and the possibility of leveraging that knowledge to design new therapies for psychiatric disorders.