Rapid antidepressant effect of ketamine correlates with astroglial plasticity in the hippocampus
This vehicle-controlled animal study (n=24) investigated the effects of esketamine (4.5mg/0.3kg) on astrocyte plasticity in the hippocampus of a depression-model rat strain. Results indicate that ketamine can rapidly modify the shape of astrocytes (sub-type of glial cells) so that they can optimally modulate the synaptic micro-environment, neurogenesis, and vascularization, which is otherwise impaired under depression.
Authors
- Ardalan, M.
- Rafati, A. H.
- Nyengaard, J. R.
Published
Abstract
Background and purpose: Astroglia contribute to the pathophysiology of major depression and antidepressant drugs act by modulating synaptic plasticity; therefore, the present study investigated whether the fast antidepressant action of ketamine is reflected in a rapid alteration of the astrocytes’ morphology in a genetic animal model of depression.Experimental Approach: S-Ketamine (15 mg·kg−1) or saline was administered as a single injection to Flinders Line (FSL/ FRL) rats. Twenty-four hours after the treatment, perfusion fixation was carried out and the morphology of glial fibrillary acid protein (GFAP)-positive astrocytes in the CA1 stratum radiatum (CA1.SR) and the molecular layer of the dentate gyrus (GCL) of the hippocampus was investigated by applying stereological techniques and analysis with Imaris software. The depressive-like behaviour of animals was also evaluated using forced swim test.Key Results: FSL rats treated with ketamine exhibited a significant reduction in immobility time in comparison with the FSL-vehicle group. The volumes of the hippocampal CA1.SR and GCL regions were significantly increased 1 day after ketamine treatment in the FSL rats. The size of astrocytes in the ketamine-treated FSL rats was larger than those in the FSL-vehicle group. Additionally, the number and length of the astrocytic processes in the CA1.SR region were significantly increased 1 day following ketamine treatment.Conclusions and Implications: Our results support the hypothesis that astroglial atrophy contributes to the pathophysiology of depression and a morphological modification of astrocytes could be one mechanism by which ketamine rapidly improves depressive behaviour.
Research Summary of 'Rapid antidepressant effect of ketamine correlates with astroglial plasticity in the hippocampus'
Introduction
Major depressive disorder is associated with structural plasticity changes in the hippocampus, and growing evidence implicates glial cells—particularly astrocytes—in the pathophysiology of depression. Astrocytes support neuronal function by supplying energy, recycling neurotransmitters and interacting with the vasculature, and preclinical work has reported stress‑related reductions in astrocyte number and soma volume in the hippocampus that may be reversed by some antidepressants. Conventional antidepressants are limited by slow onset and incomplete efficacy, whereas clinical studies show that ketamine, an NMDA receptor antagonist, can rapidly reduce depressive symptoms and suicidal ideation within hours. This study by Ardalan and colleagues set out to test whether ketamine’s rapid antidepressant-like effects are accompanied by acute morphological changes in hippocampal astrocytes. Using a genetic rat model of depression (Flinders sensitive line, FSL) and corresponding controls (Flinders resistant line, FRL), the investigators examined behaviour and multiple stereological and three-dimensional measures of astrocyte and hippocampal subregion structure 24 hours after a single dose of S‑ketamine.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- APA Citation
Ardalan, M., Rafati, A. H., Nyengaard, J. R., & Wegener, G. (2017). Rapid antidepressant effect of ketamine correlates with astroglial plasticity in the hippocampus. British Journal of Pharmacology, 174(6), 483-492. https://doi.org/10.1111/bph.13714
References (3)
Papers cited by this study that are also in Blossom
Dutta, A., Mckie, S., Deakin, J. F. W. · Psychiatry Research (2014)
Monteggia, L. M., Zarate, C. A. · Current Opinion in Neurobiology (2015)
Serafini, G., Howland, R. H., Rovedi, F. et al. · Current Neuropharmacology (2014)
Cited By (1)
Papers in Blossom that reference this study
Liu, F., Gong, Y., Wang, P. et al. · Progress in Neuro-Psychopharmacology and Biological Psychiatry (2017)
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