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Neurotrophic and Antidepressant Actions of Brain-Derived Neurotrophic Factor Require Vascular Endothelial Growth Factor
Open accessAbstract
Background Activity-dependent release of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) is essential for the rapid and sustained antidepressant actions of ketamine, and a recent study shows a similar requirement for vascular endothelial growth factor (VEGF). Since BDNF is reported to stimulate VEGF expression and/or release in neuroblastoma cells, the present study tested the hypothesis that the actions of BDNF are mediated by VEGF.Methods The role of VEGF in the antidepressant behavioral actions of BDNF was tested by intra-mPFC coinfusion of a VEGF neutralizing antibody and by neuron-specific deletion of VEGF. The influence of BDNF on the release of VEGF and the role of VEGF in the neurotrophic actions of BDNF were determined in rat primary cortical neurons. The role of BDNF in the behavioral and neurotrophic actions of VEGF was also determined.Results The results show that the rapid and sustained antidepressant-like actions of intra-mPFC BDNF are blocked by coinfusion of a VEGF neutralizing antibody, and that neuron-specific mPFC deletion of VEGF blocks the antidepressant-like actions of BDNF. Studies in primary cortical neurons demonstrate that BDNF stimulates the release of VEGF and that BDNF induction of dendrite complexity is blocked by a selective VEGF-fetal liver kinase 1 receptor antagonist. Surprisingly, the results also show reciprocal interactions, indicating that the behavioral and neurotrophic actions of VEGF are dependent on BDNF.Conclusions These findings indicate that the antidepressant-like and neurotrophic actions of BDNF require VEGF signaling, but they also demonstrate reciprocal interdependence for BDNF in the actions of VEGF.
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“mTORC1 activation appears to be driven by BDNF signaling, and in turn, mTORC1 itself might enhance BDNF production, creating a positive feedback loop that sustains neuroplasticity [75,76].”
From Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review (2024) · cites this paper as [75]
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“a single infusion of recombinant BDNF into the mPFC produces rapid and sustained antidepressant effects similar to those observed with ketamine administration [75,76]”
From Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review (2024) · cites this paper as [75]
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Metadata
- Authors
- Deyama, S., Bang, E., Kato, T., Li, X.-Y., & Duman, R. S.
- Affiliations
- Kanazawa University (JP)
- Yale University (US)
- Sumitomo Dainippon Pharma (Japan) (JP)
- Corresponding author
- Duman, Ronald S.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 86
- Issue
- 2
- Pages
- 143-152
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC6597338
- OpenAlex
- W2907856418
- Cited by
- 116
- References
- 66
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 12 · 2023: 22 · 2022: 17 · 2021: 20 · 2020: 14 · 2019: 10
- FWCI
- 7.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH045481, MH093897)
- State of Connecticut
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- brain-derived neurotrophic factor, vascular endothelial growth factor, antidepressant effects, ketamine, medial prefrontal cortex, VEGF neutralizing antibody, neurotrophic signaling
- MeSH terms
- Animals, Antidepressive Agents, Behavior, Animal, Cerebral Cortex, Male, Mice, Inbred C57BL, Microinjections, Neurons, Gene Deletion, Prefrontal Cortex, Nootropic Agents, Antibodies, Blocking, Brain-Derived Neurotrophic Factor, Vascular Endothelial Growth Factor Receptor-2, Vascular Endothelial Growth Factor A, Mice, Primary Cell Culture
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