microRNAs as novel antidepressant targets: converging effects of ketamine and electroconvulsive shock therapy in the rat hippocampus
Abstract
Early-life stress is a main contributory factor to the onset of depression. Treatments remain inadequate and as such, a large unmet medical need for novel therapeutics remains. Impeding advancement is the poor understanding of the molecular pathology. microRNAs (miRNAs) are novel regulators of gene expression. A paucity of information regarding their role in depressive pathology and antidepressant action remains. This study investigated changes to hippocampal miRNA levels induced via early-life stress in Sprague–Dawley rats and whether antidepressant treatments could reverse these changes. Investigated were the selective serotonin reuptake inhibitor fluoxetine, the rapid acting N-methyl-d-aspartate receptor antagonist ketamine and electroconvulsive shock therapy (ECT). Microarray analysis revealed early-life stress affected the expression of multiple hippocampal miRNAs. Antidepressant treatments reversed some of these effects including a stress-induced change to miR-451. Ketamine and ECT possessed the highest number of common targets suggesting convergence on common pathways. Interestingly all three treatments possessed miR-598-5p as a common target. This demonstrates that changes to hippocampal miRNA expression may represent an important component of stress-induced pathology and antidepressant action may reverse these.
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miRNAs regulate gene expression through translational repression and inhibition, and they are viable targets for intervention in neuropsychiatric disease.
“miRNAs regulate gene expression through translational repression and inhibition, and they are viable targets for intervention in neuropsychiatric disease (Issler and Chen, 2015;O'Connor et al., 2013;Scott et al., 2015).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as O'Connor et al., 2013
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- Authors
- O'Connor, R. M., Grenham, S., Dinan, T. G., & Cryan, J. F.
- Affiliations
- Department of Anatomy and Neuroscience, University College Cork, Ireland
- Alimentary Pharmabiotic Centre, University College Cork, Ireland
- Venue
- International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-09-01
- Volume
- 16
- Issue
- 8
- Pages
- 1885-1892
- ISSN
- 1469-5111
- 1461-1457
- Cited by
- 101
- References
- 3
- Language
- en
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