PMID- 22025973 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20111110 LR - 20211020 IS - 2093-3673 (Electronic) IS - 2093-3665 (Print) IS - 2093-3665 (Linking) VI - 44 IP - 3 DP - 2011 Sep TI - Modulation by the GABA(B) receptor siRNA of ethanol-mediated PKA-alpha, CaMKII, and p-CREB intracellular signaling in prenatal rat hippocampal neurons. PG - 210-7 LID - 10.5115/acb.2011.44.3.210 [doi] AB - 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 gamma-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-alpha (PKA-alpha), 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-alpha. 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. FAU - Lee, Hae Young AU - Lee HY AD - Department of Biology, College of Natural Sciences (RINS), Gyeongsang National University, Jinju, Korea. FAU - Yang, Byoung-Chul AU - Yang BC FAU - Lee, Eun-Shil AU - Lee ES FAU - Chung, Jong Ii AU - Chung JI FAU - Koh, Phil Ok AU - Koh PO FAU - Park, Moon Seok AU - Park MS FAU - Kim, Myeong Ok AU - Kim MO LA - eng PT - Journal Article DEP - 20110929 PL - Korea (South) TA - Anat Cell Biol JT - Anatomy & cell biology JID - 101531987 PMC - PMC3195825 OTO - NOTNLM OT - Ethanol OT - GABAB receptor OT - Hippocampus OT - p-CREB OT - siRNA EDAT- 2011/10/26 06:00 MHDA- 2011/10/26 06:01 PMCR- 2011/09/01 CRDT- 2011/10/26 06:00 PHST- 2011/04/20 00:00 [received] PHST- 2011/06/22 00:00 [revised] PHST- 2011/06/30 00:00 [accepted] PHST- 2011/10/26 06:00 [entrez] PHST- 2011/10/26 06:00 [pubmed] PHST- 2011/10/26 06:01 [medline] PHST- 2011/09/01 00:00 [pmc-release] AID - 10.5115/acb.2011.44.3.210 [doi] PST - ppublish SO - Anat Cell Biol. 2011 Sep;44(3):210-7. doi: 10.5115/acb.2011.44.3.210. Epub 2011 Sep 29.