Vascular endothelial growth factor-B (VEGFB) stimulates neurogenesis: Evidence from knockout mice and growth factor administration

Vascular endothelial growth factor-B (VEGFB) is an angiogenic and neuroprotective protein that reduces hypoxic and ischemic neuronal injury. To determine if VEGFB also regulates neurogenesis in the adult brain, we studied the effects of VEGFB administration in vitro and in vivo, as well as the effect of VEGFB gene knockout (KO) in mice, on bromodeoxyuridine (BrdU) incorporation and expression of immature neuronal markers in the subgranular zone (SGZ) of the hippocampal dentate gyrus and the forebrain subventricular zone (SVZ). Intracerebroventricular VEGFB administration increased BrdU incorporation into cells of neuronal lineage both in vitro and in vivo, and VEGFB-KO mice showed impaired neurogenesis, consistent with a neurogenesis-promoting effect of VEGFB. In addition, intraventricular administration of VEGFB restored neurogenesis to wild-type levels in VEGFB-KO mice. These results suggest a role for VEGFB in the regulation of adult neurogenesis, which could have therapeutic implications for diseases associated with central neuronal loss. (c) 2005 Elsevier Inc. All rights reserved.