ArticleThe international journal of neuropsychopharmacology2018
A Critical Role of Mitochondria in BDNF-Associated Synaptic Plasticity After One-Week Vortioxetine Treatment.
Article in The international journal of neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Compartment-Specific Mitochondrial Proteomic Alterations in Rat Hippocampus Following Chronic Social Isolation Stress.International journal of molecular sciences · 2026Review
- The synaptic triad in depression: how stress-related pathways converge on BDNF, NMDA receptor, and MMP-9.Pharmacological reports : PR · 2026Review
- Evaluation of Vortioxetine on Global DNA Methylation in Maternal and Offspring Rats and In Silico Molecular Docking to Key Epigenetic Enzymes.International journal of molecular sciences · 2026Article
- Withania somnifera Regulates Mitochondrial Biogenesis and Energetics in Rat Cortical Neurons: Role of BDNF and SIRT1.Molecular neurobiology · 2025Article
- Mitochondria in depression: The dysfunction of mitochondrial energy metabolism and quality control systems.CNS neuroscience & therapeutics · 2024Review
- Synaptic Microenvironment in Depressive Disorder: Insights from Synaptic Plasticity.Neuropsychiatric disease and treatment · 2021Review
- Vortioxetine administration attenuates cognitive and synaptic deficits in 5×FAD mice.Psychopharmacology · 2020Article
- Schisandra Extract and Ascorbic Acid Synergistically Enhance Cognition in Mice Through Modulation of Mitochondrial Respiration.Nutrients · 2020Article
- Changes in Hippocampal Plasticity in Depression and Therapeutic Approaches Influencing These Changes.Neural plasticity · 2020Review
- The Diagnostic Value of the Combination of Serum Brain-Derived Neurotrophic Factor and Insulin-Like Growth Factor-1 for Major Depressive Disorder Diagnosis and Treatment Efficacy.Frontiers in psychiatry · 2020Article
- Vortioxetine for Cognitive Enhancement in Major Depression: From Animal Models to Clinical Research.Frontiers in psychiatry · 2019Review
- iTRAQ-Based Quantitative Proteomics Suggests Synaptic Mitochondrial Dysfunction in the Hippocampus of Rats Susceptible to Chronic Mild Stress.Neurochemical research · 2018Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Preclinical studies have indicated that antidepressant effect of vortioxetine involves increased synaptic plasticity and promotion of spine maturation. Mitochondria dysfunction may contribute to the pathophysiological basis of major depressive disorder. Taking into consideration that vortioxetine increases spine number and dendritic branching in hippocampus CA1 faster than fluoxetine, we hypothesize that new spines induced by vortioxetine can rapidly form functional synapses by mitochondrial support, accompanied by increased brain-derived neurotrophic factor signaling. Methods: Rats were treated for 1 week with vortioxetine or fluoxetine at pharmacologically relevant doses. Number of synapses and mitochondria in hippocampus CA1 were quantified by electron microscopy. Brain-derived neurotrophic factor protein levels were visualized with immunohistochemistry. Gene and protein expression of synapse and mitochondria-related markers were investigated with real-time quantitative polymerase chain reaction and immunoblotting. Results: Vortioxetine increased number of synapses and mitochondria significantly, whereas fluoxetine had no effect after 1-week dosing. BDNF levels in hippocampus DG and CA1 were significantly higher after vortioxetine treatment. Gene expression levels of Rac1 after vortioxetine treatment were significantly increased. There was a tendency towards increased gene expression levels of Drp1 and protein levels of Rac1. However, both gene and protein levels of c-Fos were significantly decreased. Furthermore, there was a significant positive correlation between BDNF levels and mitochondria and synapse numbers. Conclusion: Our results imply that mitochondria play a critical role in synaptic plasticity accompanied by increased BDNF levels. Rapid changes in BDNF levels and synaptic/mitochondria plasticity of hippocampus following vortioxetine compared with fluoxetine may be ascribed to vortioxetine's modulation of serotonin receptors.
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