Targeting Gap Junctions: New Insights into the Treatment of Major Depressive Disorder.
Antidepressants
astrocytes
central nervous system
connexins
depressive disorder
gap junctions
hemichannels
pannexins.
Journal
Current medicinal chemistry
ISSN: 1875-533X
Titre abrégé: Curr Med Chem
Pays: United Arab Emirates
ID NLM: 9440157
Informations de publication
Date de publication:
2019
2019
Historique:
received:
02
06
2017
revised:
22
12
2017
accepted:
21
03
2018
pubmed:
29
3
2018
medline:
28
10
2019
entrez:
29
3
2018
Statut:
ppublish
Résumé
Major depressive disorder (MDD) is a multifactorial chronic and debilitating mood disease with high lifetime prevalence and associated with excess mortality. Treatments for this disease are not effective in all patients showing the need to find new therapeutic targets. This review aims to update our knowledge on 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. The method applied in this review includes a systematic compilation of the relevant literature. The use of rodent models of depression, gene analysis of hippocampal tissues of MDD patients and post-mortem studies on the brains from MDD patients suggest that astrocytic gap junction dysfunction may be a 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 a 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.
Sections du résumé
BACKGROUND
BACKGROUND
Major depressive disorder (MDD) is a multifactorial chronic and debilitating mood disease with high lifetime prevalence and associated with excess mortality. Treatments for this disease are not effective in all patients showing the need to find new therapeutic targets.
OBJECTIVE
OBJECTIVE
This review aims to update our knowledge on 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
METHODS
The method applied in this review includes a systematic compilation of the relevant literature.
RESULTS AND CONCLUSION
CONCLUSIONS
The use of rodent models of depression, gene analysis of hippocampal tissues of MDD patients and post-mortem studies on the brains from MDD patients suggest that astrocytic gap junction dysfunction may be a 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 a 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.
Identifiants
pubmed: 29589532
pii: CMC-EPUB-89313
doi: 10.2174/0929867325666180327103530
doi:
Substances chimiques
Antidepressive Agents
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
3775-3791Informations de copyright
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