News and Reviews Vascular endothelial growth factor (VEGF) and its role in the central nervous system: A new element in the neurotrophic hypothesis of antidepressant drug action Marta Maria Nowacka, Ewa Obuchowicz ⇑ Department of Pharmacology, Medical University of Silesia, Medykow 18 Street, 40-752 Katowice, Poland article info Article history: Received 7 March 2011 Accepted 20 May 2011 Available online xxxx Keywords: Vascular endothelial growth factor (VEGF) Signal transduction Neurogenesis Neuroprotection Synaptic plasticity Depression Antidepressant drugs abstract Vascular endothelial growth factor (VEGF) is a well-known cellular mitogen, and a vascular growth factor and permeability regulator. It participates in physiological and pathological processes of angiogenesis and in the development of lymphatic vessels. In addition to the proangiogenic activity, studies of recent years have revealed neurotrophic and neuroprotective potential of VEGF both in the peripheral and cen- tral nervous system. VEGF directly influences Schwann cells, neuronal progenitor cells, astrocytes and microglia. This factor plays an import role in developmental processes of the nervous tissue since it is implicated in neurogenesis and the regulation of neuronal development, and in the differentiation and formation of vessels in the brain. VEGF elicits its biological effect via an interaction with three VEGF receptor subtypes: VEGFR1, VEGFR2 and VEGFR3. In the nervous system, VEGFR2 signaling prevails. VEGF as a trophic factor, influencing both vascular endothelial cells and brain cells is a focus of the studies on neuropsychiatric disorders and psychotropic drug action. Antidepressant drugs were shown to induce hippocampal expression of VEGF. In addition, the experiments in animals models of depression have demonstrated that VEGFR2 signaling is indispensable for cellular and behavioral response to antidepres- sant drugs. Acquiring a deeper knowledge into the signaling pathways engaged in neurogenic and behav- ioral VEGF actions can unravel new targets for more efficient and quick acting antidepressant drugs. Ó 2011 Elsevier Ltd. All rights reserved. Contents 1. Introduction .......................................................................................................... 00 2. Regulation of VEGF expression ........................................................................................... 00 3. VEGF receptors ........................................................................................................ 00 4. Intracellular VEGF signal transduction in endothelial and nerve cells ............................................................ 00 5. Involvment of VEGF in the nervous system development ...................................................................... 00 6. VEGF as a neurogenesis stimulating factor .................................................................................. 00 7. The role of VEGF in synaptic plasticity ..................................................................................... 00 8. VEGF as a neuronal and glial protective factor............................................................................... 00 9. Implication of VEGF in the mechanism of action of antidepressant drug ......................................................... 00 10. Conclusions ........................................................................................................... 00 References ........................................................................................................... 00 1. Introduction Vascular endothelial growth factor (VEGF) belongs to a group of signaling proteins involved in the regulation of physiological and pathological angiogenesis. This factor increases capillary vascular permeability and is also called Vascular Permeability Factor (VPF) or vasculotropin (Brochington et al., 2004; Carmeliet and Stroke- baum, 2002; Folkman and D’Amore, 1996). The vascular permeability factor was discovered by Senger et al. in 1983 whereas 6 years later the respective gene was cloned and the protein endowed with mitogenic properties in endothelial cells 0143-4179/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.npep.2011.05.005 ⇑ Corresponding author. Tel./fax: +48 32 252 3835. E-mail address: eobuchowicz@sum.edu.pl (E. Obuchowicz). Neuropeptides xxx (2011) xxx–xxx Contents lists available at ScienceDirect Neuropeptides journal homepage: www.elsevier.com/locate/npep Please cite this article in press as: Nowacka, M.M., Obuchowicz, E. Vascular endothelial growth factor (VEGF) and its role in the central nervous system: A new element in the neurotrophic hypothesis of antidepressant drug action. Neuropeptides (2011), doi:10.1016/j.npep.2011.05.005