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. 2004 Aug;36(8):827-35.
doi: 10.1038/ng1395. Epub 2004 Jul 18.

VEGF Links Hippocampal Activity With Neurogenesis, Learning and Memory


VEGF Links Hippocampal Activity With Neurogenesis, Learning and Memory

Lei Cao et al. Nat Genet. .


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.

Comment in

  • Experiencing VEGF.
    Greenberg DA, Jin K. Greenberg DA, et al. Nat Genet. 2004 Aug;36(8):792-3. doi: 10.1038/ng0804-792. Nat Genet. 2004. PMID: 15284846 No abstract available.

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