BDNF-induced local protein synthesis and synaptic plasticity

Neuropharmacology. 2014 Jan;76 Pt C:639-56. doi: 10.1016/j.neuropharm.2013.04.005. Epub 2013 Apr 16.


Brain-derived neurotrophic factor (BDNF) is an important regulator of synaptic transmission and long-term potentiation (LTP) in the hippocampus and in other brain regions, playing a role in the formation of certain forms of memory. The effects of BDNF in LTP are mediated by TrkB (tropomyosin-related kinase B) receptors, which are known to be coupled to the activation of the Ras/ERK, phosphatidylinositol 3-kinase/Akt and phospholipase C-γ (PLC-γ) pathways. The role of BDNF in LTP is best studied in the hippocampus, where the neurotrophin acts at pre- and post-synaptic levels. Recent studies have shown that BDNF regulates the transport of mRNAs along dendrites and their translation at the synapse, by modulating the initiation and elongation phases of protein synthesis, and by acting on specific miRNAs. Furthermore, the effect of BDNF on transcription regulation may further contribute to long-term changes in the synaptic proteome. In this review we discuss the recent progress in understanding the mechanisms contributing to the short- and long-term regulation of the synaptic proteome by BDNF, and the role in synaptic plasticity, which is likely to influence learning and memory formation. This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'.

Keywords: 4EBP; A2RE; ADF; AS; Arc; BDNF; Brain-derived neurotrophic factor (BDNF); CPE; CPEB; CREB; CYFIP1; Ca(2+)- and calmodulin-dependent protein kinase II; Ca(2+)- and calmodulin-dependent protein kinase kinase; CaMKII; CaMKK; DG; E-LTP; EJC; FMRP; GIPC1; GRIP1; HFS; IEG; IP3; IRES; L-LTP; LIM domain kinase 1; LIMK1; LTP; Long-term potentiation (LTP); MAP; MAPK and ERK kinase, type 1/2; MEK1/2; MSK1; NT-4; P-bodies; PAK; PDZ (postsynaptic density-95/Discs large/zona occludens-1) domain-containing adaptor protein, type 1; PH domain; PI3-K; PICK1; PLC-γ; PSD; PSD95; PSF; Pum2; RISC; RNA processing bodies; RNA transport; RNA-induced silencing complex; Rab3a interacting molecule 1α; Rim1α; SAM68; SAP97; Src-associated in mitosis of 68 kDa; Synaptic plasticity; TORC; TRPC3; Translation; TrkB; ZBP1; actin-depolymerizing factor; activity-regulated cytoskeleton-associated protein; antisense; brain-derived neurotrophic factor; cAMP-response element-binding protein; cytoplasmic Fmr-interacting protein 1; cytoplasmic polyadenylation element; cytoplasmic polyadenylation element-binding protein; dentate gyrus; eEF; eIF; eIF4E-binding protein; early-LTP; eukaryotic elongation factor; eukaryotic initiation factor; exon junction complex; fragile X mental retardation protein; glutamate receptor-interacting protein 1; heterogeneous nuclear ribonucleoprotein; heterogeneous nuclear ribonucleoprotein (hnRNP) A2 response element; high-frequency stimulation; hnRNP; immediate-early genes; inositol 1,4,5-trisphosphate; internal ribosomal entry site; late-LTP; long-term potentiation; mRNPs; mTOR; mammalian target of rapamycin; messenger ribonucleoprotein complexes; microtubule-associated protein; mitogen- and stress-activated kinase 1; neurotrophin-4; p21-activated kinase; phosphatidylinositol 3-kinase; phospholipase C-γ; pleckstrin homology domain; polypyrimidine tract binding protein-associated splicing factor; postsynaptic density; postsynaptic density protein 95; protein interacting with C kinase 1; pumilio2; synapse-associated protein 97; target of rapamycin (TOR) complex; transient receptor-potential cation channel subfamily C (TRPC), type 3; tropomyosin-related kinase B; zipcode-binding protein 1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Humans
  • Neuronal Plasticity / physiology*
  • Protein Biosynthesis / drug effects
  • Protein Biosynthesis / physiology*
  • Receptor, trkB / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Synaptic Transmission / physiology*


  • Brain-Derived Neurotrophic Factor
  • Receptor, trkB