Talking to the Synapse: How Antidepressants Can Target Glial Cells to Reshape Brain Circuits

Functional alterations in synaptic contacts in specific brain areas are a hallmark of major depressive disorder (MDD). Antidepressant treatments not only readjust the aberrant concentrations of neurotransmitters in the synaptic clefts, but have the capacity to reshape neuronal circuits by affecting synaptogenesis and synaptic stabilization in specific regions of the brain. Nevertheless, the underlying molecular mechanisms are still unclear. Glial cells are active partners of neurons in orchestrating molecular signals that regulate the arrangement of neuronal circuits both in the developing and adult brain. Here, we present evidences indicating that glial cells might be substrates of antidepressant action for restructuring neuronal networks that has become miswired after the onset or progression of MDD. We aim to offer an alternative approach (a “gliocentric” view) to study this complex neuropsychiatric disorder and to identify alternative mechanisms of action for the currently available antidepressant therapies. Such knowledge may help to improve current treatment regimens or identify novel targets for the development of more efficacious antidepressant drugs.