proBDNF negatively regulates neuronal remodeling, synaptic transmission, and synaptic plasticity in hippocampus. Academic Article uri icon

Overview

MeSH

  • Alleles
  • Animals
  • Cells, Cultured
  • Gene Knock-In Techniques
  • Long-Term Synaptic Depression
  • Mice
  • Protein Binding
  • Protein Precursors
  • Receptor, trkB
  • Receptors, Nerve Growth Factor
  • Recombinant Fusion Proteins

MeSH Major

  • Brain-Derived Neurotrophic Factor
  • Hippocampus
  • Neuronal Plasticity
  • Synaptic Transmission

abstract

  • Experience-dependent plasticity shapes postnatal development of neural circuits, but the mechanisms that refine dendritic arbors, remodel spines, and impair synaptic activity are poorly understood. Mature brain-derived neurotrophic factor (BDNF) modulates neuronal morphology and synaptic plasticity, including long-term potentiation (LTP) via TrkB activation. BDNF is initially translated as proBDNF, which binds p75(NTR). In vitro, recombinant proBDNF modulates neuronal structure and alters hippocampal long-term plasticity, but the actions of endogenously expressed proBDNF are unclear. Therefore, we generated a cleavage-resistant probdnf knockin mouse. Our results demonstrate that proBDNF negatively regulates hippocampal dendritic complexity and spine density through p75(NTR). Hippocampal slices from probdnf mice exhibit depressed synaptic transmission, impaired LTP, and enhanced long-term depression (LTD) in area CA1. These results suggest that proBDNF acts in vivo as a biologically active factor that regulates hippocampal structure, synaptic transmission, and plasticity, effects that are distinct from those of mature BDNF. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

publication date

  • May 8, 2014

has subject area

  • Alleles
  • Animals
  • Brain-Derived Neurotrophic Factor
  • Cells, Cultured
  • Gene Knock-In Techniques
  • Hippocampus
  • Long-Term Synaptic Depression
  • Mice
  • Neuronal Plasticity
  • Protein Binding
  • Protein Precursors
  • Receptor, trkB
  • Receptors, Nerve Growth Factor
  • Recombinant Fusion Proteins
  • Synaptic Transmission

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4118923

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2014.03.040

PubMed ID

  • 24746813

Additional Document Info

start page

  • 796

end page

  • 806

volume

  • 7

number

  • 3