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neurogenesis following conditional VEGF induction in the adult brain and showed that a short episode of VEGF exposure withdrawn shortly after the generation of durable new vessels (but not under conditions where newly made vessels failed to persist) is sufficient for neurogenesis to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 language||American English|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - 29 Nov 2016|
Bibliographical noteFunding 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.
© 2016, National Academy of Sciences. All rights reserved.
- Adult neurogenesis
- Neural stem cells