Satoshi Deyama1, Eunyoung Bang2, Taro Kato3, Xiao-Yuan Li2, Ronald S Duman4. 1. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. 2. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut. 3. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., Suita, Japan. 4. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut. Electronic address: ronald.duman@yale.edu.
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.
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-mPFCBDNF 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.
Authors: Rong-Jian Liu; Francis S Lee; Xiao-Yuan Li; Francis Bambico; Ronald S Duman; George K Aghajanian Journal: Biol Psychiatry Date: 2011-10-29 Impact factor: 13.382
Authors: G Rajkowska; J J Miguel-Hidalgo; J Wei; G Dilley; S D Pittman; H Y Meltzer; J C Overholser; B L Roth; C A Stockmeier Journal: Biol Psychiatry Date: 1999-05-01 Impact factor: 13.382
Authors: Katsuya Nakamura; Kelly C Martin; Jennifer K Jackson; Kiichiro Beppu; Chan-Wook Woo; Carol J Thiele Journal: Cancer Res Date: 2006-04-15 Impact factor: 12.701
Authors: Satoshi Deyama; Eunyoung Bang; Eric S Wohleb; Xiao-Yuan Li; Taro Kato; Danielle M Gerhard; Sophie Dutheil; Jason M Dwyer; Seth R Taylor; Marina R Picciotto; Ronald S Duman Journal: Am J Psychiatry Date: 2019-01-04 Impact factor: 18.112
Authors: Olivier Berton; Colleen A McClung; Ralph J Dileone; Vaishnav Krishnan; William Renthal; Scott J Russo; Danielle Graham; Nadia M Tsankova; Carlos A Bolanos; Maribel Rios; Lisa M Monteggia; David W Self; Eric J Nestler Journal: Science Date: 2006-02-10 Impact factor: 47.728
Authors: Ashley E Lepack; Manabu Fuchikami; Jason M Dwyer; Mounira Banasr; Ronald S Duman Journal: Int J Neuropsychopharmacol Date: 2014-10-31 Impact factor: 5.176
Authors: P De Rossi; E Harde; J P Dupuis; L Martin; N Chounlamountri; M Bardin; C Watrin; C Benetollo; K Pernet-Gallay; H J Luhmann; J Honnorat; G Malleret; L Groc; A Acker-Palmer; P A Salin; C Meissirel Journal: Mol Psychiatry Date: 2016-01-05 Impact factor: 15.992