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

Licht, Tamar, Rothe, Gadiel, Kreisel, Tirzah, Wolf, Brachi, Benny, Ofra, Rooney, Alasdair G., Ffrench-Constant, Charles ORCID:, Enikolopov, Grigori and Keshet, Eli (2016) VEGF preconditioning leads to stem cell remodeling and attenuates age-related decay of adult hippocampal neurogenesis. Proceedings of the National Academy of Sciences of the United States of America, 113 (48). E7828-E7836. ISSN 0027-8424

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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neurogenesis following conditional VEGF induction in the adult brain and showed that a short episode of VEGF exposure withdrawn shortly after the generation of durable new vessels (but not under conditions where newly made vessels failed to persist) is sufficient for neurogenesis to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: Article
Additional Information: Funding Information: We thank Dr. Alexander Medvinsky (University of Edinburgh) for mice and Dr. Avi Merzel for statistical analysis. This work was supported by a European Council Research (ERC) grant [Project VASNICHE (Grant 322692)] and the Britain Israel Research and Academic Exchange Partnership.
Uncontrolled Keywords: adult neurogenesis,aging,neural stem cells,neurovascular,vegf,general ,/dk/atira/pure/subjectarea/asjc/1000
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 15 Jul 2022 14:31
Last Modified: 23 Oct 2022 03:56
DOI: 10.1073/pnas.1609592113

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