PMID- 12929140
OWN - NLM
STAT- MEDLINE
DCOM- 20031014
LR  - 20131121
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 73
IP  - 5
DP  - 2003 Sep 1
TI  - Brain-derived neurotrophic factor mitigates chronic ethanol-induced attenuation 
      of gamma-aminobutyric acid responses in cultured cerebellar granule cells.
PG  - 722-30
AB  - This study examined the effect of chronic exposure to ethanol and brain-derived 
      neurotrophic factor (BDNF) on the responsiveness of cerebellar granule cells to 
      gamma-aminobutyric acid (GABA). Cerebellar granule cell cultures were chronically 
      exposed to ethanol (100 mM), BDNF (20 ng/ml), or the combination of ethanol and 
      BDNF. Whole-cell current responses of granule cells to exogenously applied GABA 
      were monitored following at least 5 days of chronic exposure. In the 
      ethanol-treated cultures, granule cell responsiveness to GABA was attenuated. 
      Concomitant exposure of cultures to ethanol and BDNF mitigated the 
      ethanol-induced attenuation of GABA response, although BDNF, by itself, did not 
      affect responsiveness to GABA. BDNF increased the expression of the GABA(A) 
      receptor alpha6 subunit, whereas ethanol had no effect, in chronically treated 
      granule cell cultures. In addition, concomitant treatment with BDNF and ethanol 
      did not increase the expression of the GABA(A) receptor alpha6 subunit, so the 
      subunit expression alone could not account for the mitigating effect of BDNF. We 
      propose that different mechanisms regulating responsiveness to GABA underlie the 
      effects induced by ethanol and BDNF, with the former influencing the expression 
      of functional GABA(A) receptors and the latter involving the activation of the 
      TrkB receptor and its downstream signaling pathways.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Ericson, Mia
AU  - Ericson M
AD  - Department of Pharmacology and Physiology, University of Rochester Medical 
      Center, Rochester, New York 14642, USA.
FAU - Haythornthwaite, Alison R
AU  - Haythornthwaite AR
FAU - Yeh, Pamela W L
AU  - Yeh PW
FAU - Yeh, Hermes H
AU  - Yeh HH
LA  - eng
GR  - P50 AA-03510/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Protein Subunits)
RN  - 0 (Receptors, GABA-A)
RN  - 3K9958V90M (Ethanol)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Alcohol-Induced Disorders, Nervous System/physiopathology
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cells, Cultured
MH  - Central Nervous System Depressants/*pharmacology
MH  - Cerebellum/physiology
MH  - Ethanol/*pharmacology
MH  - Immunohistochemistry
MH  - Mice
MH  - Neurons/*drug effects/metabolism
MH  - Patch-Clamp Techniques
MH  - Protein Subunits/drug effects/metabolism
MH  - Receptor, trkB/metabolism
MH  - Receptors, GABA-A/drug effects/metabolism
MH  - gamma-Aminobutyric Acid/drug effects/*metabolism
EDAT- 2003/08/21 05:00
MHDA- 2003/10/15 05:00
CRDT- 2003/08/21 05:00
PHST- 2003/08/21 05:00 [pubmed]
PHST- 2003/10/15 05:00 [medline]
PHST- 2003/08/21 05:00 [entrez]
AID - 10.1002/jnr.10694 [doi]
PST - ppublish
SO  - J Neurosci Res. 2003 Sep 1;73(5):722-30. doi: 10.1002/jnr.10694.