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BDNF at the synapse: why location matters

Molecular Psychiatry volume 22, pages 1370–1375 (2017)Cite this article

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Abstract

Neurotrophic factors, a family of secreted proteins that support the growth, survival and differentiation of neurons, have been intensively studied for decades due to the powerful and diverse effects on neuronal physiology, as well as their therapeutic potential. Such efforts have led to a detailed understanding on the molecular mechanisms of neurotrophic factor signaling. One member, brain-derived neurotrophic factor (BDNF) has drawn much attention due to its pleiotropic roles in the central nervous system and implications in various brain disorders. In addition, recent advances linking the rapid-acting antidepressant, ketamine, to BDNF translation and BDNF-dependent signaling, has re-emphasized the importance of understanding the precise details of BDNF biology at the synapse. Although substantial knowledge related to the genetic, epigenetic, cell biological and biochemical aspects of BDNF biology has now been established, certain aspects related to the precise localization and release of BDNF at the synapse have remained obscure. A recent series of genetic and cell biological studies have shed light on the question—the site of BDNF release at the synapse. In this Perspectives article, these new insights will be placed in the context of previously unresolved issues related to BDNF biology, as well as how BDNF may function as a downstream mediator of newer pharmacological agents currently under investigation for treating psychiatric disorders.

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Acknowledgements

We gratefully acknowledge support from the National Research Foundation of Korea (NRF) - NRF-2016R1D1A1B03934438 [M.S.], Ministry of Science, ICT and Future Planning (MSIP) - No. 2231-415 [M.S.], Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) - MH105592 [K.M.], Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) - NS052819 [F.S.L], New York Community Trust (NYCT) [F.S.L].

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  1. Department of Structure and Function of Neural Network, Synaptic Circuit Plasticity Laboratory, Korea Brain Research Institute, Dong-gu, Daegu, Korea

    M Song

  2. Lieber Institute for Brain Development, Baltimore, MD, USA

    K Martinowich

  3. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    K Martinowich

  4. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    K Martinowich

  5. Department of Psychiatry, Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College of Cornell University, New York, NY, USA

    F S Lee

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Song, M., Martinowich, K. & Lee, F. BDNF at the synapse: why location matters. Mol Psychiatry 22, 1370–1375 (2017). https://doi.org/10.1038/mp.2017.144

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