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首页> 外文期刊>Alcohol >Ethanol inhibits brain-derived neurotrophic factor stimulation of extracellular signal-regulated/mitogen-activated protein kinase in cerebellar granule cells.
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Ethanol inhibits brain-derived neurotrophic factor stimulation of extracellular signal-regulated/mitogen-activated protein kinase in cerebellar granule cells.

机译：乙醇抑制小脑颗粒细胞中细胞外信号调节/促分裂原活化蛋白激酶的脑源性神经营养因子刺激。

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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.
机译：脑源性神经营养因子（BDNF）已成为神经元发育和突触可塑性的重要介体。 BDNF激活多个通过磷酸化，转录和翻译调节细胞功能的信号转导级联反应。已知乙醇会抑制神经营养蛋白信号传导，但是尚未对发育中的神经元中乙醇对BDNF信号传导的作用进行彻底的药理分析。进行这些实验以确定神经元中细胞外信号调节蛋白激酶（ERK）活化的膜去极化，BDNF浓度和乙醇浓度之间的相互作用。我们检查了体外3天后在生理（5mM）或升高（25mM）钾培养条件下生长的小脑颗粒细胞。 BDNF在10分钟内刺激ERK磷酸化（pERK），并在20至60分钟内支持刺激。在两种情况下，乙醇均会降低基础pERK并降低BDNF刺激ERK的幅度。 NMDA受体拮抗剂2-amino-5-phosphonovalerate不会影响基底pERK或抑制ER的BDNF刺激，这表明NMDA受体在短期培养中不会调节BDNF刺激ERK。这些数据表征了乙醇对生长因子信号转导的药理作用，并为进一步表征乙醇抑制ERK的生化机制提供了模型基础。乙醇对BDNF信号转导的干扰可能是乙醇暴露导致的一些认知缺陷和发育异常的基础。

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