Abstract
Pro–brain-derived neurotrophic factor (proBDNF) and mature BDNF utilize distinct receptors to mediate divergent neuronal actions. Using new tools to quantitate endogenous BDNF isoforms, we found that mouse neurons secrete both proBDNF and mature BDNF. The highest levels of proBDNF and p75 were observed perinatally and declined, but were still detectable, in adulthood. Thus, BDNF actions are developmentally regulated by secretion of proBDNF or mature BDNF and by local expression of p75 and TrkB.
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Acknowledgements
We thank K. Teng and members of the Hempstead laboratory for their input. These studies were supported by grants from the National Institute of Neurological Disorders and Stroke (NS30687 to B.L.H. and NS52819 to F.S.L.), National 973 Basic Research Program of China (No. 2006CB503803 and 2009CB941403 to Z.-Y.C.) and the Intramural Program of the National Institute of Child Health and Human Development and the National Institute of Mental Health (to B.L.).
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C.-J.S., T.M., K.M., Z.-Y.C., W.M. and L.T. generated the Bdnf-HA mouse; G.N., B.L. and J.Y. generated and characterized the pro-domain antibody; J.Y., G.N. and D.J. performed the experiments; and B.L.H., B.L., F.S.L. and J.Y. designed the experiments and wrote the manuscript.
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Yang, J., Siao, CJ., Nagappan, G. et al. Neuronal release of proBDNF. Nat Neurosci 12, 113–115 (2009). https://doi.org/10.1038/nn.2244
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DOI: https://doi.org/10.1038/nn.2244
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