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siRNA‐mediated GABA B receptor at early fetal rat brain upon acute and chronic ethanol exposure: Down regulation of PKA and p‐CREB expression
Author(s) -
Naseer M.I.,
Lee H.Y.,
Ullah N.,
Ullah I.,
Park M.S.,
Kim M.O.
Publication year - 2011
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20824
Subject(s) - creb , baclofen , chemistry , medicine , endocrinology , pharmacology , receptor , biochemistry , agonist , biology , transcription factor , gene
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‐α) 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. Synapse, 2011. © 2010 Wiley‐Liss, Inc.