Glial Purinergic Signals and Psychiatric Disorders

Schuichi Koizumi

doi:10.3389/fncel.2021.822614

Abstract

Emotion-related neural networks are regulated in part by the activity of glial cells, and glial dysfunction can be directly related to emotional diseases such as depression. Here, we discuss three different therapeutic strategies involving astrocytes that are effective for treating depression. First, the antidepressant, fluoxetine, acts on astrocytes and increases exocytosis of ATP. This has therapeutic effects via brain-derived neurotrophic factor-dependent mechanisms. Second, electroconvulsive therapy is a well-known treatment for drug-resistant depression. Electroconvulsive therapy releases ATP from astrocytes to induce leukemia inhibitory factors and fibroblast growth factor 2, which leads to antidepressive actions. Finally, sleep deprivation therapy is well-known to cause antidepressive effects. Sleep deprivation also increases release of ATP, whose metabolite, adenosine, has antidepressive effects. These independent treatments share the same mechanism, i.e., ATP release from astrocytes, indicating an essential role of glial purinergic signals in the pathogenesis of depression.

Highlights

The human brain is estimated to contain ∼100 billion neurons, which are connected by more than 1014 synapses to form complex neuronal networks
We explored the molecular pathogenesis of depression by assessing the common features of effective therapeutic drugs and methods for treating depression
We identified astrocyte phenomena commonly induced by the antidepressants FLX, Electroconvulsive therapy (ECT), and sleep deprivation (SD), and concluded that increased levels of ATPo is a common mechanism

Summary

Introduction

The human brain is estimated to contain ∼100 billion neurons, which are connected by more than 1014 synapses to form complex neuronal networks. We review abnormalities in communication between astrocytes and neurons via extracellular ATP (ATPo) and discuss this within the context of the molecular pathology of depression. Glial cells express various neurotransmitter receptors, ion channels, and transporters, and have the ability to transmit information by releasing chemicals such as ATP (Koizumi et al, 2003), which are linked to Ca2+ excitability.

Results

Conclusion