Targeting Gap Junctions: New Insights in the Treatment of Major Depressive Disorder.

BACKGROUND Major depressive disorder (MDD) is a multifactorial chronic and debilitating mood disease with high lifetime prevalence and associated with excess mortality. Treatments of this disease are not effective in all patients showing the need to find new therapeutic targets. OBJECTIVE This review aims to update our knowledge about the involvement of astroglial gap junctions and hemichannels in MDD and to show how they have become potential targets for the treatment of this pathology. METHODS The method applied in this review includes a systematic compilation of the relevant literature. RESULTS AND CONCLUSION The use of rodent models of depression, gene analysis of hippocampal tissues of MDD patients and post-mortem studies of brains from MDD patients suggest that astrocytic gap junction dysfunction may be part of MDD etiologies. Chronic antidepressant treatments of rats, rat cultured cortical astrocytes and human astrocytoma cell lines support the hypothesis that the up-regulation of gap junctional coupling between astrocytes could be an underlying mechanism for the therapeutic effect of antidepressants. However, two recent functional studies suggest that connexin43 hemichannel activity is part of several antidepressants mode of action and that astrocyte gap junctional intercellular communication and hemichannels exert different effects on antidepressant drug response. Even if they emerge as new therapeutic targets for new and more active treatments, further studies are needed to decipher the sophisticated and respective role of astrocytic gap junctions and hemichannels in MDD.

• Publication year

  2019

• Venue

  Current Medicinal Chemistry

• Publication date

  2019-05-31

• Fields of study

  Medicine

• Identifiers
  DOI 10.2174/0929867325666180327103530PMID 29589532
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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