Role of vascular endothelial growth factor in adult hippocampal neurogenesis: Implications for the pathophysiology and treatment of depression

It is now well established that the adult brain has the capacity to generate new neurons throughout life. Although the functional significance of adult neurogenesis still remains to be established, increasing evidence has implicated compromised hippocampal neurogenesis as a possible contributor in the development of major depressive disorder. Antidepressants increase hippocampal neurogenesis and there is evidence in rodent models that the therapeutic efficacy of these agents is attributable, in part, to this neurogenic effect. As such, considerable interest has been directed at identifying molecular signals, including neurotrophic factors and related signaling pathways that are associated with antidepressant action and could operate as key modulators in the regulation of neurogenesis in the adult hippocampus. One interesting candidate is vascular endothelial growth factor (VEGF), which is known to possess strong neurogenic effects. In this review, we will discuss the involvement of VEGF signaling in the etiology and treatment of depression.

► Stress decreases and antidepressant treatment increases VEGF levels in limbic structures of the brain, most notably hippocampus.
► VEGF is necessary and sufficient for the neurogenic and behavioral actions of antidepressant treatments.
► Rapid and robust induction of VEGF expression can increase the proliferation of quiescent neural progenitor cells, and lead to a robust increase in neurogenesis.