Editors' ChoiceNeuroscience

Cheering Up with VEGF

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Science's STKE  20 Mar 2007:
Vol. 2007, Issue 378, pp. tw91
DOI: 10.1126/stke.3782007tw91

Although the molecular mechanisms of antidepressant action remain unclear, one hypothesis suggests that stimulation of growth factor signaling and of adult neurogenesis in the hippocampus may be implicated in their effects. Warner-Schmidt and Duman investigated the effects of different classes of antidepressants on hippocampal expression of the neurotrophic and pro-angiogenic factor VEGF (vascular endothelial growth factor), which their research group had previously shown to be enhanced by electroconvulsive seizure (ECS) treatment. The abundance of VEGF mRNA increased in the hippocampal granule cell layer of rats treated for 14 days with fluoxetine (a serotonin reuptake inhibitor) or desipramine (a norepinephrine reuptake inhibitor), as did the abundance of VEGF in hippocampal homogenates. Pharmacological blockade of the VEGF receptor Flk-1 inhibited the increase in cell proliferation in the hippocampal subgranular zone (SGZ) produced by ECS or chronic exposure to fluoxetine or desipramine, whereas intracerebroventricular delivery of a VEGF isoform stimulated SGZ cell proliferation. Furthermore, pharmacological blockade of Flk-1 inhibited the effects of desipramine on rat behavioral responses in chronic and subchronic models of antidepressant treatment, whereas VEGF had an antidepressant-like effect. Thus, the authors conclude that VEGF plays a key role in mediating both behavioral effects of several classes of antidepressants and their effects on SGZ cell proliferation. Noting that antidepressants promoted the proliferation of hippocampal endothelial cells as well as hippocampal neurogenesis, the authors speculated that this could play a role in the treatment of certain forms of depression that are associated with vascular abnormalities.

J. L. Warner-Schmidt, R. S. Duman, VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants. Proc. Natl. Acad. Sci. U.S.A. 104, 4647-4652 (2007). [Abstract] [Full Text]

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