PMID- 24068823
OWN - NLM
STAT- MEDLINE
DCOM- 20131125
LR  - 20220408
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 33
IP  - 39
DP  - 2013 Sep 25
TI  - The ability of BDNF to modify neurogenesis and depressive-like behaviors is 
      dependent upon phosphorylation of tyrosine residues 365/367 in the 
      GABA(A)-receptor gamma2 subunit.
PG  - 15567-77
LID - 10.1523/JNEUROSCI.1845-13.2013 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) is a potent regulator of neuronal 
      activity, neurogenesis, and depressive-like behaviors; however, downstream 
      effectors by which BDNF exerts these varying actions remain to be determined. 
      Here we reveal that BDNF induces long-lasting enhancements in the efficacy of 
      synaptic inhibition by stabilizing gamma2 subunit-containing GABA(A) receptors 
      (GABA(A)Rs) at the cell surface, leading to persistent reductions in neuronal 
      excitability. This effect is dependent upon enhanced phosphorylation of tyrosines 
      365 and 367 (Y365/7) in the GABA(A)R gamma2 subunit as revealed using mice in which 
      these residues have been mutated to phenyalanines (Y365/7F). Heterozygotes for 
      this mutation exhibit an antidepressant-like phenotype, as shown using 
      behavioral-despair models of depression. In addition, heterozygous Y365/7F mice 
      show increased levels of hippocampal neurogenesis, which has been strongly 
      connected with antidepressant action. Both the antidepressant phenotype and the 
      increased neurogenesis seen in these mice are insensitive to further modulation 
      by BDNF, which produces robust antidepressant-like activity and neurogenesis in 
      wild-type mice. Collectively, our results suggest a critical role for GABA(A)R gamma2 
      subunit Y365/7 phosphorylation and function in regulating the effects of BDNF.
FAU - Vithlani, Mansi
AU  - Vithlani M
AD  - Department of Neuroscience, Physiology and Pharmacology, University College 
      London, London WC1E 6BT, United Kingdom, Department of Neuroscience, Tufts 
      University, Boston, Massachusetts 02111, AstraZeneca Pharmaceuticals, Cambridge, 
      Massachusetts 02139, and Department of Physiology and Biophysics, University at 
      Buffalo, State University of New York, Buffalo, New York 14214.
FAU - Hines, Rochelle M
AU  - Hines RM
FAU - Zhong, Ping
AU  - Zhong P
FAU - Terunuma, Miho
AU  - Terunuma M
FAU - Hines, Dustin J
AU  - Hines DJ
FAU - Revilla-Sanchez, Raquel
AU  - Revilla-Sanchez R
FAU - Jurd, Rachel
AU  - Jurd R
FAU - Haydon, Phillip
AU  - Haydon P
FAU - Rios, Maribel
AU  - Rios M
FAU - Brandon, Nicholas
AU  - Brandon N
FAU - Yan, Zhen
AU  - Yan Z
FAU - Moss, Stephen J
AU  - Moss SJ
LA  - eng
GR  - NS037585/NS/NINDS NIH HHS/United States
GR  - MH085774/MH/NIMH NIH HHS/United States
GR  - R01 MH097446/MH/NIMH NIH HHS/United States
GR  - R01 NS051195/NS/NINDS NIH HHS/United States
GR  - MH095385/MH/NIMH NIH HHS/United States
GR  - DK073311/DK/NIDDK NIH HHS/United States
GR  - R37 NS037585/NS/NINDS NIH HHS/United States
GR  - R01 NS056359/NS/NINDS NIH HHS/United States
GR  - NS081735/NS/NINDS NIH HHS/United States
GR  - MH084233/MH/NIMH NIH HHS/United States
GR  - NS056359/NS/NINDS NIH HHS/United States
GR  - R01 MH085774/MH/NIMH NIH HHS/United States
GR  - R01 MH095385/MH/NIMH NIH HHS/United States
GR  - NS051195/NS/NINDS NIH HHS/United States
GR  - CAPMC/CIHR/Canada
GR  - R01 DK073311/DK/NIDDK NIH HHS/United States
GR  - R01 MH084233/MH/NIMH NIH HHS/United States
GR  - MH097446/MH/NIMH NIH HHS/United States
GR  - R01 NS037585/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Gabrg2 protein, mouse)
RN  - 0 (Protein Subunits)
RN  - 0 (Receptors, GABA-A)
RN  - 42HK56048U (Tyrosine)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology/therapeutic use
MH  - Depression/*drug therapy/genetics
MH  - Heterozygote
MH  - Hippocampus/cytology/metabolism/physiology
MH  - Inhibitory Postsynaptic Potentials/drug effects/genetics
MH  - Mice
MH  - Mutation, Missense
MH  - Neurogenesis/*drug effects/genetics
MH  - Neurons/cytology/*metabolism/physiology
MH  - Phenotype
MH  - Phosphorylation
MH  - Protein Subunits/genetics/metabolism
MH  - Protein Transport/drug effects
MH  - Receptors, GABA-A/genetics/*metabolism
MH  - Tyrosine/genetics/metabolism
PMC - PMC3782626
EDAT- 2013/09/27 06:00
MHDA- 2013/12/16 06:00
PMCR- 2014/03/25
CRDT- 2013/09/27 06:00
PHST- 2013/09/27 06:00 [entrez]
PHST- 2013/09/27 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
PHST- 2014/03/25 00:00 [pmc-release]
AID - 33/39/15567 [pii]
AID - 1845-13 [pii]
AID - 10.1523/JNEUROSCI.1845-13.2013 [doi]
PST - ppublish
SO  - J Neurosci. 2013 Sep 25;33(39):15567-77. doi: 10.1523/JNEUROSCI.1845-13.2013.