microRNAs as novel antidepressant targets: converging effects of ketamine and electroconvulsive shock therapy in the rat hippocampus
Richard M. O'Connor, Susan Grenham, Timothy G Dinan, John F Cryan
The International Journal of Neuropsychopharmacology September 1, 2013 DOI: 10.1017/s1461145713000448 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Sprague-Dawley rats exposed to early-life stress |
| Interventions | Fluoxetine Ketamine Electroconvulsive shock therapy (ECT) |
| Measures | Microarray analysis |
| Topics | Esketamine Ketamine |
| Key findings | Early-life stress altered the expression of multiple hippocampal microRNAs in rats, and treatment with fluoxetine, ketamine, or electroconvulsive shock therapy reversed some of these changes, including a stress-induced change to miR-451. Ketamine and ECT shared the highest number of common targets, and all three treatments targeted miR-598-5p, which the authors suggest indicates convergence on common pathways and that hippocampal miRNA changes may contribute to stress-induced pathology and antidepressant action. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 4
- Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective Psychiatry and Clinical Neurosciences June 19, 2019
- miR-98-5p plays a critical role in depression and antidepressant effect of ketamine Translational Psychiatry September 3, 2021
- Macrophage Migration Inhibitory Factor and microRNA-451a in Response to Mindfulness-based Therapy or Treatment as Usual in Patients with Depression, Anxiety, or Stress and Adjustment Disorders The International Journal of Neuropsychopharmacology January 10, 2018
- Epigenetic mechanisms of rapid-acting antidepressants Translational Psychiatry September 4, 2024
Cites 4
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Glutamatergic Modulators: The Future of Treating Mood Disorders? Harvard Review of Psychiatry August 1, 2010
- NMDA Receptor Blockade at Rest Triggers Rapid Behavioural Antidepressant Responses Nature June 15, 2011