VEGF as a potential target for therapeutic intervention in depression

Abstract

Antidepressants are among the most widely prescribed drugs, however the mechanism underlying their therapeutic efficacy is not known. Neurotrophic factors represent a promising class of targets for antidepressant treatments. We recently characterized a role for vascular endothelial growth factor (VEGF) in cellular and behavioral antidepressant responses. VEGF is a potent mitogen and survival factor for endothelial cells (ECs) and neurons, and modulator of synaptic transmission. Because VEGF has been implicated in a variety of diseases, understanding the molecular and cellular specificity of antidepressant-induced VEGF will be crucial to determine its potential as a therapeutic target in depression.

Figures

Figure 1. Antidepressants and stress differentially regulate VEGF expression, neurogenesis, and depression-related behaviors

In the dentate gyrus of the hippocampus, antidepressants increase VEGF mRNA and protein expression in granule cell layer (GCL) neurons (grey circles) and endothelial cells (EC) (white ovals), stimulating proliferation of EC and neuronal precursor cells (NPC) (black circles) in the subgranular zone (SGZ). Induction of VEGF expression is required for antidepressant behavioral responses in both neurogenesis dependent and neurogenesis independent paradigms, suggesting that VEGF also exerts its effects through additional cellular mechanisms, such as neural plasticity. NSF=novelty suppressed feeding; CUS=chronic unpredictable stress; FST=forced swim test; TST=tail suspension test; LH=Learned Helplessness.