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.
This is a preview of subscription content
Access options
Subscribe to Journal
Get full journal access for 1 year
68,37 €
only 5,70 € per issue
Tax calculation will be finalised during checkout.
Buy article
Get time limited or full article access on ReadCube.
$32.00
All prices are NET prices.


References
Huang, E.J. & Reichardt, L.F. Annu. Rev. Neurosci. 24, 677–736 (2001).
Rex, C.S. et al. J. Neurosci. 27, 3017–3029 (2007).
Chen, Z.Y. et al. J. Neurosci. 25, 6156–6166 (2005).
Mowla, S.J. et al. J. Biol. Chem. 276, 12660–12666 (2001).
Kolarow, R., Brigadski, T. & Lessmann, V. J. Neurosci. 27, 10350–10364 (2007).
Teng, H.K. et al. J. Neurosci. 25, 5455–5463 (2005).
Woo, N.H. et al. Nat. Neurosci. 8, 1069–1077 (2005).
Yan, Q. et al. Neuroscience 78, 431–448 (1997).
Matsumoto, T. et al. Nat. Neurosci. 11, 131–133 (2008).
Tsirka, S.E., Guslandris, A., Amaral, D.G. & Strickland, S. Nature 377, 340–344 (1995).
Adachi, N., Kohara, K. & Tsumoto, T. BMC Neurosci. 6, 42–52 (2005).
Wu, Y.J. et al. J. Neurosci. Res. 75, 825–834 (2004b).
Zheng, M., Streck, R.D., Scott, R.E., Seidah, N.G. & Pintar, J.E. J. Neurosci. 14, 4656–4673 (1994).
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.).
Author information
Affiliations
Contributions
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.
Corresponding author
Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–3 and Supplementary Methods (PDF 4534 kb)
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nn.2244
Further reading
-
Synucleinopathy-associated pathogenesis in Parkinson’s disease and the potential for brain-derived neurotrophic factor
npj Parkinson's Disease (2021)
-
Emergence of local and global synaptic organization on cortical dendrites
Nature Communications (2021)
-
Long-term depression at hippocampal mossy fiber-CA3 synapses involves BDNF but is not mediated by p75NTR signaling
Scientific Reports (2021)
-
Comparative Genomics of the BDNF Gene, Non-Canonical Modes of Transcriptional Regulation, and Neurological Disease
Molecular Neurobiology (2021)
-
Neurobiology of BDNF in fear memory, sensitivity to stress, and stress-related disorders
Molecular Psychiatry (2020)