Lee Hae Young, Yang Byoung-Chul, Lee Eun-Shil, Chung Jong Ii, Koh Phil Ok, Park Moon Seok, Kim Myeong Ok
Department of Biology, College of Natural Sciences (RINS), Gyeongsang National University, Jinju, Korea.
Anat Cell Biol. 2011 Sep;44(3):210-7. doi: 10.5115/acb.2011.44.3.210. Epub 2011 Sep 29.
Fetal alcohol syndrome (FAS) is a developmental neuropathology resulting from in utero exposure to ethanol; many of ethanol's effects are likely to be mediated by the neurotransmitter γ-aminobutyric acid (GABA). We studied modulation of the neurotransmitter receptor GABA(B)R and its capacity for intracellular signal transduction under conditions of ethanol treatment (ET) and RNA interference to investigate a potential role for GABA signaling in FAS. ET increased GABA(B1)R protein levels, but decreased protein kinase A-α (PKA-α), calcium/calmodulin-dependent protein kinase II (CaMKII) and phosphorylation of cAMP-response element binding protein (p-CREB), in cultured hippocampal neurons harvested at gestation day 17.5. To elucidate GABA(B1)R response to ethanol, we observed the effects of a GABA(B)R agonist and antagonist in pharmacotherapy for ethanol abuse. Baclofen increased GABA(B)R, CaMKII and p-CREB levels, whereas phaclofen decreased GABA(B)R, CaMKII and p-CREB levels except PKA-α. Furthermore, when GABA(B1)R was knocked down by siRNA treatment, CaMKII and p-CREB levels were reduced upon ET. We speculate that stimulation of GABA(B1)R activity by ET can modulate CaMKII and p-CREB signaling to detrimental effect on fetal brain development.
胎儿酒精综合征（FAS）是一种因子宫内暴露于乙醇而导致的发育性神经病理学疾病；乙醇的许多作用可能是由神经递质γ-氨基丁酸（GABA）介导的。我们研究了在乙醇处理（ET）和RNA干扰条件下神经递质受体GABA(B)R的调节及其细胞内信号转导能力，以探讨GABA信号在FAS中的潜在作用。在妊娠第17.5天收获的培养海马神经元中，ET增加了GABA(B1)R蛋白水平，但降低了蛋白激酶A-α（PKA-α）、钙/钙调蛋白依赖性蛋白激酶II（CaMKII）和环磷酸腺苷反应元件结合蛋白的磷酸化水平（p-CREB）。为了阐明GABA(B1)R对乙醇的反应，我们观察了GABA(B)R激动剂和拮抗剂在乙醇滥用药物治疗中的作用。巴氯芬增加了GABA(B)R、CaMKII和p-CREB水平，而法氯芬降低了GABA(B)R、CaMKII和p-CREB水平，但PKA-α除外。此外，当通过siRNA处理敲低GABA(B1)R时，ET后CaMKII和p-CREB水平降低。我们推测，ET对GABA(B1)R活性的刺激可调节CaMKII和p-CREB信号，对胎儿脑发育产生有害影响。
