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Biosynthesis and processing of endogenous BDNF: CNS neurons store and secrete BDNF, not pro-BDNF

Abstract

Pro- and mature BDNF activate very different receptors and intracellular pathways, potentially leading to either neuronal death or survival. Here we examined the biochemistry of endogenous BDNF in mouse neurons using sensitive reagents and found that pro-BDNF is rapidly converted intracellularly to mature BDNF, the latter being stored and released by excitatory input.

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Figure 1: Detection of BDNF in the mouse hippocampus.
Figure 2: Intracellular processing of pro-BDNF in neurons.
Figure 3: BDNF is necessary for inducing hippocampal CA3 to CA1 LTP, but not LTD.

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Acknowledgements

We thank S. Wiese and M. Sendtner for the floxed BDNF line and the BDNF antibodies, B. Fayard for constructs, and V. Crotet for technical assistance. T.M. was supported by the Uehara Memorial Foundation and by the Mochida Memorial Foundation for Medical and Pharmaceutical Research and M.K. by the Deutsche Forschungsgemeinschaft.

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Contributions

S.R. generated the cBdnf mutant mice. J.K. and R.K. generated the Bdnf-Myc mutant mice. M.P. and M.K. carried out the electrophysiology. T.M. and Y.-A.B. designed and carried out all of the other experiments, and wrote the manuscript.

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Correspondence to Yves-Alain Barde.

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Supplementary Figures 1 and 2, and Methods (PDF 159 kb)

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Matsumoto, T., Rauskolb, S., Polack, M. et al. Biosynthesis and processing of endogenous BDNF: CNS neurons store and secrete BDNF, not pro-BDNF. Nat Neurosci 11, 131–133 (2008). https://doi.org/10.1038/nn2038

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