With more than 350 million depressed individuals worldwide, major depressive disorder is one of the most common psychiatric illnesses. Although, the pathophysiology of depression is far from being fully understood, five decades of development of different classes of antidepressants targeting central monoaminergic systems (serotonin, noradrenaline and dopamine) has led to the emergence of the monoaminergic hypothesis. However, despite a growing number of available pharmacotherapies, treatment of major depression nevertheless remains unsatisfactory.
The astroglial system plays a crucial role in the mechanisms of action of DBS. Accordingly, the antidepressant-like response induced by DBS is counteracted by a pharmacological lesion of astrocytes in the stimulated area. Two mechanistic hypotheses have been proposed to explain the astrocytic modulation of the neuronal response induced by DBS . First, the “shrinking hypothesis” suggests that astrocytes, by releasing adenosine in response to DBS, activate neuronal A1 receptors resulting in a shortening of the width of action potentials. Second, the “ceiling hypothesis” proposes that astrocytes, by actively pumping K+ ions from the extracellular spaces, prevent the establishment of the “depolarization-like blockade” of the neuronal membrane. Both events are directed to an optimal functioning of pyramidal neurons that are still capable of following high frequency stimulations induced by DBS. Lastly as a translational outcome, we have proposed that an unaltered neuronal–glial system constitutes a major prerequisite to optimize antidepressant DBS efficacy, and that decreasing the frequency of DBS would increase the antidepressant response of partial responders.
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The Role of Astroglia in the Antidepressant Action of Deep Brain Stimulation
Front. Cell. Neurosci., 12 January 2016 | http://dx.doi.org/10.3389/fncel.2015.00509