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BDNF promotes differentiation and maturation of adult-born neurons through GABAergic transmission

Academic Article
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Overview

authors

  • Waterhouse, E. G.
  • An, J. J.
  • Orefice, L. L.
  • Baydyuk, M.
  • Liao, G. Y.
  • Zheng, K.
  • Lu, B.
  • Xu, Baoji

publication date

  • October 2012

journal

  • Journal of Neuroscience  Journal

abstract

  • Brain-derived neurotrophic factor (BDNF) has been implicated in regulating adult neurogenesis in the subgranular zone (SGZ) of the dentate gyrus; however, the mechanism underlying this regulation remains unclear. In this study, we found that Bdnf mRNA localized to distal dendrites of dentate gyrus granule cells isolated from wild-type (WT) mice, but not from Bdnf(klox/klox) mice where the long 3' untranslated region (UTR) of Bdnf mRNA is truncated. KCl-induced membrane depolarization stimulated release of dendritic BDNF translated from long 3' UTR Bdnf mRNA in cultured hippocampal neurons, but not from short 3' UTR Bdnf mRNA. Bdnf(klox/klox) mice exhibited reduced expression of glutamic acid decarboxylase 65 (a GABA synthase), increased proliferation of progenitor cells, and impaired differentiation and maturation of newborn neurons in the SGZ. These deficits in adult neurogenesis were rescued with administration of phenobarbital, an enhancer of GABA(A) receptor activity. Furthermore, we observed similar neurogenesis deficits in mice where the receptor for BDNF, TrkB, was selectively abolished in parvalbumin (PV)-expressing GABAergic interneurons. Thus, our data suggest that locally synthesized BDNF in dendrites of granule cells promotes differentiation and maturation of progenitor cells in the SGZ by enhancing GABA release, at least in part, from PV-expressing GABAergic interneurons.

subject areas

  • Age Factors
  • Animals
  • Brain-Derived Neurotrophic Factor
  • Cell Differentiation
  • Cells, Cultured
  • Female
  • Hippocampus
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Neural Stem Cells
  • Neurogenesis
  • Rats
  • Rats, Sprague-Dawley
  • Synaptic Transmission
  • Up-Regulation
  • gamma-Aminobutyric Acid
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Identity

PubMed Central ID

  • PMC3519245

International Standard Serial Number (ISSN)

  • 0270-6474

Digital Object Identifier (DOI)

  • 10.1523/jneurosci.0709-12.2012

PubMed ID

  • 23055503
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Additional Document Info

start page

  • 14318

end page

  • 14330

volume

  • 32

issue

  • 41

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