Modulation by the GABAB receptor siRNA of ethanol-mediated PKA-alpha, CaMKII, and p-CREB intracellular signaling in prenatal rat hippocampal neurons.
10.5115/acb.2011.44.3.210
- Author:
Hae Young LEE
1
;
Byoung Chul YANG
;
Eun Shil LEE
;
Jong Ii CHUNG
;
Phil Ok KOH
;
Moon Seok PARK
;
Myeong Ok KIM
Author Information
1. Department of Biology, College of Natural Sciences (RINS), Gyeongsang National University, Jinju, Korea. mokim@gnu.ac.kr
- Publication Type:Original Article
- Keywords:
GABAB receptor;
siRNA;
Ethanol;
Hippocampus;
p-CREB
- MeSH:
Animals;
Baclofen;
Brain;
Calcium-Calmodulin-Dependent Protein Kinase Type 2;
Carrier Proteins;
Ethanol;
Fetal Alcohol Syndrome;
gamma-Aminobutyric Acid;
Hippocampus;
Neurons;
Neurotransmitter Agents;
Phosphorylation;
Pregnancy;
Protein Kinases;
Rats;
Receptors, Neurotransmitter;
RNA Interference;
RNA, Small Interfering;
Signal Transduction
- From:Anatomy & Cell Biology
2011;44(3):210-217
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 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-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 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-alpha. 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.
