Ethanol exposure can cause various negative effects on embryo’s nervous system during pregnancy. Especially ethanol was known to induce mental retardation, learning disability, movement disorder, and epilepsy leading to the fetal alcohol syndrome (FAS). As the inhibitory neurotransmitter gamma amino...
Ethanol exposure can cause various negative effects on embryo’s nervous system during pregnancy. Especially ethanol was known to induce mental retardation, learning disability, movement disorder, and epilepsy leading to the fetal alcohol syndrome (FAS). As the inhibitory neurotransmitter gamma aminobutyric acid (GABA) modulates ethanol consumption, alcohol withdrawal symptoms and seizure generation by interacting with the GABAB receptor that is G-protein coupled receptor 1. In the present study, we have studied the change of GABAB1 receptor, protein kinase A-α (PKA- α) and phosphorylation of cAMP-response element binding protein (p-CREB) on in vitro ethanol exposure and chronic ethanol exposure at pregnant female, by using a system where GABAB1 receptors were specifically knocked down in the in vitro cultivated hippocampus from gestational day (GD) 17.5 fetal rat. Also, the effect of GABAB receptor agonist and antagonist was observed to elucidate the possible reversing roles of GABAB receptor in pharmacotherapy for ethanol abuse. On directly in vitro ethanol treatment, ethanol induced that GABAB1 receptor protein expression increased, and p-CREB levels were decreased, But on directly in vitro ethanol treatment after maternal chronic ethanol treatment, ethanol-induced decreased GABAB1 receptor increased p-CREB with chronic ethanol treatment. Also, Baclofen increased p-CREB level which was decreased by both in vitro ethanol exposure and chronic ethanol exposure. During directly in vitro ethanol treatment, induced GABAB1 receptor protein can decreased by siRNA treatment, which confirmed that p-CREB level was similar to normal level, but p-CREB level was dramatically decreased by GABAB1 siRNA at in vitro ethanol after maternal chronic ethanol treatment. Also, during ethanol treatment, we know that siRNA disturb medicinal effect because our data have opposite level’s change in medical effect by siRNA, and GABAB1 receptor siRNA induced to knock down p-CREB but not PKA-α. Also, our result shows that these changes are not follow these patterns during directly ethanol exposure in the cell, so we expected that directly ethanol exposure may change the pathway. In conclusion, we found that reduced p-CREB level by increased GABAB1 receptor was reverse to the control of p-CREB by using GABAB1R siRNA at directly in vitro ethanol treatment. But, they have the other pattern at in vitro ethanol treatment after chronic ethanol exposure during pregnancy. Also, GABAB receptor agonist, baclofen, induced GABAB1R expression and partially effect on p-CREB expression which was relative neuroprotection. Finally, GABAB receptor has no modulation of PKA-α but it activates the other second messenger which modulates p-CREB.
Ethanol exposure can cause various negative effects on embryo’s nervous system during pregnancy. Especially ethanol was known to induce mental retardation, learning disability, movement disorder, and epilepsy leading to the fetal alcohol syndrome (FAS). As the inhibitory neurotransmitter gamma aminobutyric acid (GABA) modulates ethanol consumption, alcohol withdrawal symptoms and seizure generation by interacting with the GABAB receptor that is G-protein coupled receptor 1. In the present study, we have studied the change of GABAB1 receptor, protein kinase A-α (PKA- α) and phosphorylation of cAMP-response element binding protein (p-CREB) on in vitro ethanol exposure and chronic ethanol exposure at pregnant female, by using a system where GABAB1 receptors were specifically knocked down in the in vitro cultivated hippocampus from gestational day (GD) 17.5 fetal rat. Also, the effect of GABAB receptor agonist and antagonist was observed to elucidate the possible reversing roles of GABAB receptor in pharmacotherapy for ethanol abuse. On directly in vitro ethanol treatment, ethanol induced that GABAB1 receptor protein expression increased, and p-CREB levels were decreased, But on directly in vitro ethanol treatment after maternal chronic ethanol treatment, ethanol-induced decreased GABAB1 receptor increased p-CREB with chronic ethanol treatment. Also, Baclofen increased p-CREB level which was decreased by both in vitro ethanol exposure and chronic ethanol exposure. During directly in vitro ethanol treatment, induced GABAB1 receptor protein can decreased by siRNA treatment, which confirmed that p-CREB level was similar to normal level, but p-CREB level was dramatically decreased by GABAB1 siRNA at in vitro ethanol after maternal chronic ethanol treatment. Also, during ethanol treatment, we know that siRNA disturb medicinal effect because our data have opposite level’s change in medical effect by siRNA, and GABAB1 receptor siRNA induced to knock down p-CREB but not PKA-α. Also, our result shows that these changes are not follow these patterns during directly ethanol exposure in the cell, so we expected that directly ethanol exposure may change the pathway. In conclusion, we found that reduced p-CREB level by increased GABAB1 receptor was reverse to the control of p-CREB by using GABAB1R siRNA at directly in vitro ethanol treatment. But, they have the other pattern at in vitro ethanol treatment after chronic ethanol exposure during pregnancy. Also, GABAB receptor agonist, baclofen, induced GABAB1R expression and partially effect on p-CREB expression which was relative neuroprotection. Finally, GABAB receptor has no modulation of PKA-α but it activates the other second messenger which modulates p-CREB.
Keyword
#GABAB1 receptor ethanol pathways hippocampal neurons by siRNA prenatal
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