The Effects of Chronic Alcohol Exposure and Histone Deacetylase Inhibition on GABA-A Receptor Subunit Expression in the Rat Cortex
Session Number
Q804
Advisor(s)
Subhash Pandey, University of Illinois at Chicago Tara Teppen, University of Illinois at Chicago
Location
B-108
Start Date
28-4-2016 11:05 AM
End Date
28-4-2016 11:30 AM
Abstract
The changes in gamma amino butyric acid-A (GABA-A) receptor function have been shown during acute and chronic ethanol exposure and its withdrawal. However, the changes in the mRNA levels of the GABA-A receptor subunits are less clear. In addition, ethanol withdrawal after chronic ethanol exposure shows an increase in histone deacetylase (HDAC) activity in the rat amygdala. We measured the gene expression of certain GABA-A receptor subunits (α1, α4, α5, and δ) in the prefrontal cortex of chronic ethanol and withdrawal rat groups using the Quantitative Real-Time Polymerase Chain Reaction. Cohorts of the control and withdrawal groups were treated with suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor, in order to test whether changes in HDAC levels would alter transcription of the GABAA receptor subunits. It was observed that chronic ethanol exposure upregulated mRNA levels of the α5 subunit, which returned to normal levels during withdrawal. Transcriptional levels of other subunits were not significantly altered by ethanol treatment or withdrawal. The SAHA treatment during withdrawal did not alter the expression of any subunits of the GABA-A receptors. These results, although preliminary in nature, may suggest an important role for the α5 subunit in the dysregulation of GABA-A receptors during alcohol dependence.
The Effects of Chronic Alcohol Exposure and Histone Deacetylase Inhibition on GABA-A Receptor Subunit Expression in the Rat Cortex
B-108
The changes in gamma amino butyric acid-A (GABA-A) receptor function have been shown during acute and chronic ethanol exposure and its withdrawal. However, the changes in the mRNA levels of the GABA-A receptor subunits are less clear. In addition, ethanol withdrawal after chronic ethanol exposure shows an increase in histone deacetylase (HDAC) activity in the rat amygdala. We measured the gene expression of certain GABA-A receptor subunits (α1, α4, α5, and δ) in the prefrontal cortex of chronic ethanol and withdrawal rat groups using the Quantitative Real-Time Polymerase Chain Reaction. Cohorts of the control and withdrawal groups were treated with suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor, in order to test whether changes in HDAC levels would alter transcription of the GABAA receptor subunits. It was observed that chronic ethanol exposure upregulated mRNA levels of the α5 subunit, which returned to normal levels during withdrawal. Transcriptional levels of other subunits were not significantly altered by ethanol treatment or withdrawal. The SAHA treatment during withdrawal did not alter the expression of any subunits of the GABA-A receptors. These results, although preliminary in nature, may suggest an important role for the α5 subunit in the dysregulation of GABA-A receptors during alcohol dependence.