PMID- 20506568
OWN - NLM
STAT- MEDLINE
DCOM- 20110401
LR  - 20131121
IS  - 1098-2396 (Electronic)
IS  - 0887-4476 (Linking)
VI  - 65
IP  - 2
DP  - 2011 Feb
TI  - siRNA-mediated GABA(B) receptor at early fetal rat brain upon acute and chronic 
      ethanol exposure: down regulation of PKA and p-CREB expression.
PG  - 109-18
LID - 10.1002/syn.20824 [doi]
AB  - To observe the modulatory role of GABA(B1)R upon ethanol's effect during early 
      brain development, we studied the effects of chronic maternal (10% ethanol during 
      pregnancy) and acute (in vitro) ethanol exposure on the neuronal protein kinase A 
      (PKA-alpha) and phosphorylation of cAMP-response element binding protein (p-CREB), 
      using a system where GABA(B1)R were specifically knocked down in the primary 
      cells cultured at gestational day (GD) 12.5. The results showed that upon acute 
      and chronic ethanol treatment the GABA(B1)R expression was decreased and further 
      decreased when GABA(B1)R was transfection with siRNA, while increased upon 
      exposure of baclofen, and baclofen plus phaclofen treatment. PKA expression was 
      also decreased with acute and chronic ethanol treatment, whereas it showed 
      increase upon exposure of baclofen and baclofen with phaclofen. Furthermore, 
      intracellular Ca(2+) concentration was increased upon ethanol, baclofen, 
      phaclofen exposure but showed decrease in GABA(B1)R siRNA group. Finally, these 
      effects could lead to changes of p-CREB expression, which showed same expression 
      pattern as PKA. We speculate that GABA(B)R activity upon ethanol exposure could 
      modulate intracellular calcium homeostasis and the expressional changes of PKA 
      and p-CREB, which cause various negative effects on fetal brain development and 
      modulation of GABA(B)R upon ethanol exposure may underlying cause of ethanol's 
      effects.
CI  - Copyright (c) 2010 Wiley-Liss, Inc.
FAU - Naseer, M I
AU  - Naseer MI
AD  - Division of Life Science, College of Natural Sciences (RINS) and Applied Life 
      Science (BK21), Gyeongsang National University, Chinju 660-701, Republic of 
      Korea. mimrannaseer@yahoo.com.
FAU - Lee, H Y
AU  - Lee HY
FAU - Ullah, N
AU  - Ullah N
FAU - Ullah, I
AU  - Ullah I
FAU - Park, M S
AU  - Park MS
FAU - Kim, M O
AU  - Kim MO
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Synapse
JT  - Synapse (New York, N.Y.)
JID - 8806914
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, GABA-B)
RN  - 3K9958V90M (Ethanol)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Brain/cytology/*drug effects/embryology
MH  - CREB-Binding Protein/genetics/*metabolism
MH  - Calcium/metabolism
MH  - Cells, Cultured
MH  - Central Nervous System Depressants/*administration & dosage
MH  - Cyclic AMP-Dependent Protein Kinases/genetics/*metabolism
MH  - Down-Regulation/*drug effects
MH  - Embryo, Mammalian
MH  - Ethanol/*administration & dosage
MH  - Female
MH  - Neurons/drug effects
MH  - Pregnancy
MH  - RNA, Small Interfering/genetics/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, GABA-B/genetics/*metabolism
MH  - Time Factors
MH  - Transfection/methods
EDAT- 2010/05/28 06:00
MHDA- 2011/04/02 06:00
CRDT- 2010/05/28 06:00
PHST- 2010/05/28 06:00 [entrez]
PHST- 2010/05/28 06:00 [pubmed]
PHST- 2011/04/02 06:00 [medline]
AID - 10.1002/syn.20824 [doi]
PST - ppublish
SO  - Synapse. 2011 Feb;65(2):109-18. doi: 10.1002/syn.20824.