Astroglial 5-HT_2B receptor in mood disorders

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-HT_2B receptors. Activation of these receptors triggers numerous intracellular signaling cascades that regulate expression of multiple genes. Astroglial 5-HT_2B 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-HT_2B 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:

• Astrocyte
• 5-HT_2B receptor
• fluoxetine
• gene expression
• major depression
• Parkinson’s disease-associated depression

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was supported by Grant No. 31171036 to LP, No. 31400925 to DS and No. 31000479 to BL from the National Natural Science Foundation of China.