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KMID : 1237720110440030210
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Anatomy & Cell Biology
2011 Volume.44 No. 3 p.210 ~ p.217
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Modulation by the GABAB receptor siRNA of ethanol-mediated PKA-α, CaMKII, and p-CREB intracellular signaling in prenatal rat hippocampal neurons
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Lee Hae-Young
Lee Eun-Shil
Park Moon-Seok
Kim Myeong-Ok
Yang Byoung-Chul
Chung Jong-Il
Koh Phil-Ok
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Abstract
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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 GABABR 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 GABAB1R 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 GABAB1R response to ethanol, we observed the effects of a GABABR agonist and antagonist in pharmacotherapy for ethanol abuse. Baclofen increased GABABR, CaMKII and p-CREB levels, whereas phaclofen decreased GABABR, CaMKII and p-CREB levels except PKA-α. Furthermore, when GABAB1R was knocked down by siRNA treatment, CaMKII and p-CREB levels were reduced upon ET. We speculate that stimulation of GABAB1R activity by ET can modulate CaMKII and p-CREB signaling to detrimental effect on fetal brain development.
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KEYWORD
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GABAB receptor, siRNA, Ethanol, Hippocampus, p-CREB
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