title: VEGF links hippocampal activity with neurogenesis, learning and memory.
abstract: An enriched environment is associated with hippocampal plasticity, including improved cognitive performance and increased neurogenesis. Here, we show that hippocampal expression of vascular endothelial growth factor (VEGF) is increased by both an enriched environment and performance in a spatial maze. Hippocampal gene transfer of VEGF in adult rats resulted in approximately 2 times more neurogenesis associated with improved cognition. In contrast, overexpression of placental growth factor, which signals through Flt1 but not kinase insert domain protein receptors (KDRs), had negative effects on neurogenesis and inhibited learning, although it similarly increased endothelial cell proliferation. Expression of a dominant-negative mutant KDR inhibited basal neurogenesis and impaired learning. Coexpression of mutant KDR antagonized VEGF-enhanced neurogenesis and learning without inhibiting endothelial cell proliferation. Furthermore, inhibition of VEGF expression by RNA interference completely blocked the environmental induction of neurogenesis. These data support a model in which VEGF, acting through KDR, mediates the effect of the environment on neurogenesis and cognition.
authors.affiliation: Department of Neurological Surgery, Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Jiao
authors.forename: David S
authors.initials: DS
authors.lastname: Zuzga
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Liu
authors.forename: Dahna M
authors.initials: DM
authors.lastname: Fong
authors.forename: Deborah
authors.initials: D
authors.lastname: Young
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: During
mesh_terms: D000818:Animals; D002455:Cell Division; D004730:Endothelium, Vascular / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D007858:Learning; D008568:Memory; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000502:physiology; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
chemical_list: C000608038:Pgf protein, rat; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor