PMID- 23089626
OWN - NLM
STAT- MEDLINE
DCOM- 20130531
LR  - 20211021
IS  - 1876-7753 (Electronic)
IS  - 1873-5061 (Print)
IS  - 1873-5061 (Linking)
VI  - 10
IP  - 1
DP  - 2013 Jan
TI  - BDNF profoundly and specifically increases KCNQ4 expression in neurons derived 
      from embryonic stem cells.
PG  - 29-35
LID - S1873-5061(12)00083-9 [pii]
LID - 10.1016/j.scr.2012.08.005 [doi]
AB  - Neurons resembling the spiral ganglion neurons (SGNs) of the auditory nerve can 
      be generated from embryonic stem cells through induced overexpression of the 
      transcription factor Neurogenin-1 (Neurog1). While recapitulating this 
      developmental pathway produces glutamatergic, bipolar neurons reminiscent of 
      SGNs, these neurons are functionally immature, being characterized by a 
      depolarized resting potential and limited excitability. We explored the effects 
      of two neurotrophins known to be present in the inner ear, brain derived 
      neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), on the electrophysiology of 
      neurons following Neurog1 induction. Our data reveal a significant reduction in 
      resting membrane potential (RMP) following neurotrophin exposure, with BDNF 
      producing a more robust effect than NT-3. This effect was accompanied by a 
      profound and specific upregulation of the KCNQ4 subtype, where a 9-fold increase 
      was observed with quantitative PCR. The other neuronally expressed KCNQ subtypes 
      (2, 3, and 5) exhibited upregulation which was 3-fold or less in magnitude. 
      Quantitative immunohistochemistry confirmed the increase in KCNQ4 expression at 
      the protein level. The present data show a novel link between BDNF and KCNQ4 
      expression, yielding insight into the restricted expression pattern of a channel 
      known to play special roles in setting the resting potential of auditory cells 
      and in the etiology of progressive high-frequency hearing loss.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Purcell, Erin K
AU  - Purcell EK
AD  - The University of Michigan, Ann Arbor, MI 48109, USA. erinfred@umich.edu
FAU - Yang, Amy
AU  - Yang A
FAU - Liu, Liqian
AU  - Liu L
FAU - Velkey, J Matthew
AU  - Velkey JM
FAU - Morales, Marti M
AU  - Morales MM
FAU - Duncan, R Keith
AU  - Duncan RK
LA  - eng
GR  - R01 NS048187/NS/NINDS NIH HHS/United States
GR  - P30 DC005188/DC/NIDCD NIH HHS/United States
GR  - T32DC00011/DC/NIDCD NIH HHS/United States
GR  - GM069985/GM/NIGMS NIH HHS/United States
GR  - P20 GM069985/GM/NIGMS NIH HHS/United States
GR  - T32 DC000011/DC/NIDCD NIH HHS/United States
GR  - NS04187/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120905
PL  - England
TA  - Stem Cell Res
JT  - Stem cell research
JID - 101316957
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (KCNQ Potassium Channels)
RN  - 0 (Kcnq4 protein, mouse)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neurotrophin 3)
RN  - 182238-50-2 (Neurog1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cell Differentiation
MH  - Cell Line
MH  - Embryonic Stem Cells/cytology/*drug effects/metabolism
MH  - KCNQ Potassium Channels/*metabolism
MH  - Membrane Potentials/drug effects
MH  - Mice
MH  - Nerve Tissue Proteins/*metabolism
MH  - Neurons/cytology/*metabolism/pathology
MH  - Neurotrophin 3/pharmacology
PMC - PMC3525722
MID - NIHMS406742
EDAT- 2012/10/24 06:00
MHDA- 2013/06/01 06:00
PMCR- 2014/01/01
CRDT- 2012/10/24 06:00
PHST- 2012/03/21 00:00 [received]
PHST- 2012/08/15 00:00 [revised]
PHST- 2012/08/27 00:00 [accepted]
PHST- 2012/10/24 06:00 [entrez]
PHST- 2012/10/24 06:00 [pubmed]
PHST- 2013/06/01 06:00 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - S1873-5061(12)00083-9 [pii]
AID - 10.1016/j.scr.2012.08.005 [doi]
PST - ppublish
SO  - Stem Cell Res. 2013 Jan;10(1):29-35. doi: 10.1016/j.scr.2012.08.005. Epub 2012 
      Sep 5.