Astrocyte, a Promising Target for Mood Disorder Interventions

Abstract

Mood disorders have multiple phenotypes and complex underlying biological mechanisms and, as such, there are no effective therapeutic strategies. A review of recent work on the role of astrocytes in mood disorders is thus warranted, which we embark on here. We argue that there is tremendous potential for novel strategies for therapeutic interventions based on the role of astrocytes. Astrocytes are traditionally considered to have supporting roles within the brain, yet emerging evidence has shown that astrocytes have more direct roles in influencing brain function. Notably, evidence from postmortem human brain tissues has highlighted changes in glial cell morphology, density and astrocyte-related biomarkers and genes following mood disorders, indicating astrocyte involvement in mood disorders. Findings from animal models strongly imply that astrocytes not only change astrocyte morphology and physiological characteristics but also influence neural circuits via synapse structure and formation. This review pays particular attention to interactions between astrocytes and neurons and argues that astrocyte dysfunction affects the monoaminergic system, excitatory-inhibitory balance and neurotrophic states of local networks. Together, these studies provide a foundation of knowledge about the exact role of astrocytes in mood disorders. Importantly, we then change the focus from neurons to glial cells and the interactions between the two, so that we can understand newly proposed mechanisms underlying mood disorders, and to identify more diagnostic indicators or effective targets for treatment of these diseases.

Keywords: anxiety disorder; astrocytes; depression; gliotransmitters; neuron.

FIGURE 1

(A) Astrocytes can take up, metabolize, and recycle glutamate that is released into the synapses. (B) In depression and anxiety disorder conditions, astrocyte dysfunction may lead to excitatory–inhibitory imbalance within neural networks.