Anatomy and Cell Biology

Korean Association of Anatomists (대한해부학회)
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Modulation by the $GABA_{B}$ receptor siRNA of ethanol-mediated PKA-${\alpha}$, CaMKII, and p-CREB intracellular signaling in prenatal rat hippocampal neurons

  • Lee, Hae-Young (Department of Biology, College of Natural Sciences (RINS), Gyeongsang National University) ;
  • Yang, Byoung-Chul (National Institute of Animal Science) ;
  • Lee, Eun-Shil (Department of Biology, College of Natural Sciences (RINS), Gyeongsang National University) ;
  • Chung, Jong-Ii (Department of Agronomy, Research Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University) ;
  • Koh, Phil-Ok (Department of Anatomy, Research Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University) ;
  • Park, Moon-Seok (Department of Biology, College of Natural Sciences (RINS), Gyeongsang National University) ;
  • Kim, Myeong-Ok (Department of Biology, College of Natural Sciences (RINS), Gyeongsang National University)
  • Published : 2011.09.30
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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 $GABA_{B}R$ 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.

Keywords

References

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