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Editorial
. 2017 Oct;22(10):1370-1375.
doi: 10.1038/mp.2017.144. Epub 2017 Jul 25.

BDNF at the synapse: why location matters

M Song  1 , K Martinowich  2   3   4 , F S Lee  5
Affiliations
Editorial

BDNF at the synapse: why location matters

M Song et al. Mol Psychiatry. 2017 Oct.

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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Conflict of interest statement

Disclosure: The authors declare no conflict of interest.

Figures

Figure 1
Figure 1. BDNF and its receptors at the mature synapse
Schematic of synapse showing localization of BDNF and its receptors in presynaptic, postsynaptic neuronal compartments, as well as from astrocytes and microglia. BDNF is stored in dense core vesicles (DCV) in the presynaptic compartment. The storage organelle for BDNF in the other synaptic components has not been identified. Conventional antidepressants (such as SSRI) elevate presynaptic BDNF, while ketamine has been postulated to enhance postsynaptic BDNF protein translation. While neurons express full-length TrkB as well as truncated TrkB with developmental and pathologically changing levels, non-neuronal cells mainly exhibit expression of truncated TrkB.–
See this image and copyright information in PMC

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