Ethanol inhibits brain-derived neurotrophic factor stimulation of extracellular signal-regulated/mitogen-activated protein kinase in cerebellar granule cells.
Alcohol
; 39(1): 29-37, 2006 May.
Article
en En
| MEDLINE
| ID: mdl-16938627
ABSTRACT
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.
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Bases de datos:
MEDLINE
Asunto principal:
Cerebelo
/
Factor Neurotrófico Derivado del Encéfalo
/
Quinasas MAP Reguladas por Señal Extracelular
/
Etanol
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Alcohol
Asunto de la revista:
TRANSTORNOS RELACIONADOS COM SUBSTANCIAS
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos