PMID- 16938627
OWN - NLM
STAT- MEDLINE
DCOM- 20061006
LR  - 20150813
IS  - 0741-8329 (Print)
IS  - 0741-8329 (Linking)
VI  - 39
IP  - 1
DP  - 2006 May
TI  - Ethanol inhibits brain-derived neurotrophic factor stimulation of extracellular 
      signal-regulated/mitogen-activated protein kinase in cerebellar granule cells.
PG  - 29-37
AB  - Brain-derived neurotrophic factor (BDNF) has emerged as a prominent mediator of 
      neuronal development and synaptic plasticity. BDNF activates multiple signal 
      transduction cascades that regulate cellular function through phosphorylation, 
      transcription, and translation. Ethanol is known to inhibit neurotrophin 
      signaling, but a thorough pharmacological analysis of the effect of ethanol on 
      BDNF signaling in developing neurons has not been performed. These experiments 
      were undertaken to determine the interactions between membrane depolarization, 
      BDNF concentration, and ethanol concentration on extracellular signal-regulated 
      protein kinase (ERK) activation in neurons. We examined cerebellar granule cells 
      grown under physiological (5mM) or elevated (25mM) potassium culture conditions 
      after 3 days in vitro. BDNF-stimulated ERK phosphorylation (pERK) within 10min 
      and supported stimulation from 20 to 60min. Ethanol decreased basal pERK and 
      reduced the magnitude of BDNF stimulation of ERK under both conditions. The NMDA 
      receptor antagonist 2-amino-5-phosphonovalerate did not effect basal pERK or 
      inhibit BDNF stimulation of ERK, suggesting that NMDA receptors do not modulate 
      BDNF stimulation of ERK in short-term cultures. These data characterize the 
      pharmacological effects of ethanol on growth factor signaling and provide the 
      basis of a model for further characterization of the biochemical mechanisms of 
      ERK inhibition by ethanol. Perturbation of BDNF signal transduction by ethanol 
      may underlie some of the cognitive deficits and developmental abnormalities 
      resulting from ethanol exposure.
FAU - Ohrtman, Joshua D
AU  - Ohrtman JD
AD  - Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, 
      National Institute on Alcohol Abuse and Alcoholism, National Institutes of 
      Health, 5625 Fisher's Lane MSC 9411, Bethesda, MD 20892-9411, USA.
FAU - Stancik, Elizabeth K
AU  - Stancik EK
FAU - Lovinger, David M
AU  - Lovinger DM
FAU - Davis, Margaret I
AU  - Davis MI
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20060728
PL  - United States
TA  - Alcohol
JT  - Alcohol (Fayetteville, N.Y.)
JID - 8502311
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 3K9958V90M (Ethanol)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/antagonists & 
      inhibitors/pharmacology/*physiology
MH  - Cerebellum/*cytology/drug effects/*enzymology
MH  - Enzyme Activation/drug effects
MH  - Ethanol/*pharmacology
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Neurons/drug effects/enzymology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
EDAT- 2006/08/30 09:00
MHDA- 2006/10/07 09:00
CRDT- 2006/08/30 09:00
PHST- 2006/03/08 00:00 [received]
PHST- 2006/06/16 00:00 [revised]
PHST- 2006/06/20 00:00 [accepted]
PHST- 2006/08/30 09:00 [pubmed]
PHST- 2006/10/07 09:00 [medline]
PHST- 2006/08/30 09:00 [entrez]
AID - S0741-8329(06)00108-X [pii]
AID - 10.1016/j.alcohol.2006.06.011 [doi]
PST - ppublish
SO  - Alcohol. 2006 May;39(1):29-37. doi: 10.1016/j.alcohol.2006.06.011. Epub 2006 Jul 
      28.