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

Tamar Licht, Gadiel Rothe, Tirzah Kreisel, Brachi Wolf, Ofra Benny, Alasdair G. Rooney, Charles Ffrench-Constant, Grigori Enikolopov, Eli Keshet*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

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neurogenesis following conditional VEGF induction in the adult brain and showed that a short episode of VEGF exposure withdrawn shortly after the generation of durable new vessels (but not under conditions where newly made vessels failed to persist) is sufficient for neurogenesis to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.

Original languageAmerican English
Pages (from-to)E7828-E7836
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number48
DOIs
StatePublished - 29 Nov 2016

Bibliographical note

Publisher Copyright:
© 2016, National Academy of Sciences. All rights reserved.

Keywords

  • Adult neurogenesis
  • Aging
  • Neural stem cells
  • Neurovascular
  • VEGF

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