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Cited by 116Treatment of Major DepressionNerve injury and regenerationNeurotransmitter Receptor Influence on Behavior

Neurotrophic and Antidepressant Actions of Brain-Derived Neurotrophic Factor Require Vascular Endothelial Growth Factor

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Deyama, Satoshi, Bang, Eunyoung, Kato, Taro, Li, Xiao-Yuan, Duman, Ronald S.·2019·Biological Psychiatry
DOI 10.1016/j.biopsych.2018.12.014PMC PMC6597338
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Abstract

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 is driven by BDNF signaling and might enhance BDNF production, creating a positive feedback loop that sustains neuroplasticity.

    “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]

    The Discussion (page unavailable) cites evidence that BDNF stimulates VEGF expression and release through an mTORC1 pathway. The Results and Discussion describe reciprocal BDNF–VEGF signaling, but do not say that mTORC1 enhances BDNF production or establishes the claimed mTORC1–BDNF feedback loop. (LLM, conf=0.84)

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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.

    “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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Research works printed but not linked: 1

  1. [22]Qi XR, Zhao J, Liu J, Fang H, Swaab DF, Zhou JN (2015): Abnormal retinoid and TrkB signaling in the prefrontal cortex in mood disorders. Cereb Cortex 25: 75– 83. 23960204

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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.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2019-07
Volume
86
Issue
2
Pages
143-152
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2018.12.014
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
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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 › 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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