VEGF preconditioning leads to stem cell remodeling and attenuates age-related decay of adult hippocampal neurogenesis

Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):E7828-E7836. doi: 10.1073/pnas.1609592113. Epub 2016 Nov 14.


Several factors are known to enhance adult hippocampal neurogenesis but a factor capable of inducing a long-lasting neurogenic enhancement that attenuates age-related neurogenic decay has not been described. Here, we studied hippocampal neurogenesis following conditional VEGF induction in the adult brain and showed that a short episode of VEGF exposure withdrawn shortly after the generation of durable new vessels (but not under conditions where newly made vessels failed to persist) is sufficient for neurogenesis to proceed at a markedly elevated level for many months later. Continual neurogenic increase over several months was not accompanied by accelerated exhaustion of the neuronal stem cell (NSC) reserve, thereby allowing neurogenesis to proceed at a markedly elevated rate also in old mice. Neurogenic enhancement by VEGF preconditioning was, in part, attributed to rescue of age-related NSC quiescence. Remarkably, VEGF caused extensive NSC remodelling manifested in transition of the enigmatic NSC terminal arbor onto long cytoplasmic processes engaging with and spreading over even remote blood vessels, a configuration reminiscent of early postnatal "juvenile" NSCs. Together, these findings suggest that VEGF preconditioning might be harnessed for long-term neurogenic enhancement despite continued exposure to an "aged" systemic milieu.

Keywords: VEGF; adult neurogenesis; aging; neural stem cells; neurovascular.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Animals
  • Cell Shape
  • Cerebrovascular Circulation
  • Dentate Gyrus / blood supply
  • Dentate Gyrus / cytology*
  • Dentate Gyrus / physiology
  • Female
  • Gene Expression
  • Male
  • Mice, Transgenic
  • Neural Stem Cells / physiology*
  • Neurogenesis*
  • Stem Cell Niche
  • Vascular Endothelial Growth Factor A / physiology*


  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse