Astroglial 5-HT2B receptor in mood disorders

Expert Rev Neurother. 2018 May;18(5):435-442. doi: 10.1080/14737175.2018.1458612. Epub 2018 Mar 30.

Abstract

Introduction: Astroglia represent the main cellular homeostatic system of the central nervous system (CNS). Astrocytes are intimately involved in regulation and maintenance of neurotransmission by regulating neurotransmitters removal and turnover and by supplying neurons with neurotransmitters precursors. Astroglial cells are fundamental elements of monoaminergic transmission in the brain and in the spinal cord. Astrocytes receive monoaminergic inputs and control catabolism of monoamines through dedicated transporters and intracellular enzymatic pathways.Areas covered: Astroglial cells express serotonergic receptors; in this review, we provide an in-depth characterization of 5-HT2B receptors. Activation of these receptors triggers numerous intracellular signaling cascades that regulate expression of multiple genes. Astroglial 5-HT2B receptors are activated by serotonin-specific reuptake inhibitors, such as major anti-depressant fluoxetine. Expression of astroglial serotonin receptors undergoes remarkable changes in depression disorders, and these changes can be corrected by chronic treatment with anti-depressant drugs.Expert commentary: Depressive behaviors, which occur in rodents following chronic stress or in neurotoxic models of Parkinson disease, are associated with significant changes in the expression of astroglial, but not neuronal 5-HT2B receptors; while therapy with anti-depressants normalizes both receptors expression and depressive behavioral phenotype. In summary, astroglial serotonin receptors are linked to mood disorders and may represent a novel target for cell- and molecule-specific therapies of depression and mood disorders.

Keywords: 5-HT2B receptor; Astrocyte; Parkinson’s disease-associated depression; fluoxetine; gene expression; major depression.