Targeting astrocytes in major depression

Abstract

Astrocytes represent a highly heterogeneous population of neural cells primarily responsible for the homeostasis of the CNS. Astrocytes express multiple receptors for neurotransmitters, including the serotonin 5-HT_2B receptors and interact with neurones at the synapse. Astroglia contribute to neurological diseases through homeostatic response, neuroprotection and reactivity. In major depression, astrocytes show signs of degeneration and are decreased in numbers, which may lead to a misbalance in neurotransmission and aberrant synaptic connectivity. In this review, we summarize astroglia-specific effects of major antidepressants and outline future strategies for astroglia-specific therapy in neuropsychiatric disorders.

Keywords:

• astrocytes
• major depression
• mechanism of drug action
• neuropsychiatric diseases
• serotonin-specific reuptake inhibitors

Financial & competing interests disclosure

This study was supported by Grant No. 31171036 to L Peng from the National Natural Science Foundation of China. A Verkhratsky was supported in part by the grant (agreement from August 27 2013 № 02.В.49.21.0003) between The Ministry of Education and Science of the Russian Federation and Lobachevsky State University of Nizhny Novgorod and by the grant of the Russian Scientific Foundation №14-15-00633. The authors have no other 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 apart from those disclosed.

Key issues

• Astrocytes are highly heterogeneous population of specialized neural cells responsible for homeostasis and defense of the CNS.

• Astrocytes undergo morphological and functional atrophy in major depression, which may contribute to neurotransmission displacement and hence to pathological progression.

• Antidepressant drugs affect astroglial biochemistry and physiology, which may represent a part of the therapeutic action.

• Specific targeting of astroglia may be regarded as a novel strategy in developing antidepressant drugs.