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

Licht, T., Rothe, G., Kreisel, T., Wolf, B., Benny, O., Rooney, A. G., Ffrench-Constant, C., Enikolopov, G., Keshet, E. (November 2016) VEGF preconditioning leads to stem cell remodeling and attenuates age-related decay of adult hippocampal neurogenesis. Proc Natl Acad Sci U S A, 113 (48). E7828-E7836. ISSN 1091-6490 (Electronic)0027-8424 (Linking)

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URL: https://www.ncbi.nlm.nih.gov/pubmed/27849577
DOI: 10.1073/pnas.1609592113

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neurogenesis following conditional VEGF induction in the adult brain and showed that a short episode of VEGF exposure withdrawn shortly after the generation of durable new vessels (but not under conditions where newly made vessels failed to persist) is sufficient for neurogenesis to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

Item Type: Paper
Uncontrolled Keywords: Vegf adult neurogenesis aging neural stem cells neurovascular
Subjects: organs, tissues, organelles, cell types and functions > tissues types and functions > hippocampus
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > neurogenesis
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
CSHL Authors:
Communities: CSHL labs > Enikopolov lab
Depositing User: Matt Covey
Date: 14 November 2016
Date Deposited: 29 Nov 2016 17:29
Last Modified: 08 Nov 2017 19:19
PMCID: PMC5137765
Related URLs:
URI: http://repository.cshl.edu/id/eprint/33906

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