TY - JOUR
T1 - Comparison of chronic ethanol and chronic intermittent ethanol treatments on the expression of GABAA and NMDA receptor subunits
AU - Sheela Rani, C. S.
AU - Ticku, Maharaj K.
N1 - Funding Information:
We thank Mr. Jason Hernandez for technical assistance and Dr. Ashok K. Mehta for critical reading of the manuscript. This work was supported by a grant to MKT from the National Institute of Alcohol Abuse and Alcoholism grant # AA 10552.
PY - 2006/2
Y1 - 2006/2
N2 - We examined the mRNA and protein levels of GABAA and NMDA receptor (NMDAR) subunits in cultured mouse cortical neurons following exposure to chronic ethanol (CE) or chronic intermittent ethanol (CIE), and after 5 days of withdrawal. With respect to GABAA receptor mRNA, both treatments decreased the levels of α1 and α2 subunits, and increased the level of α4. However, only CE treatment caused parallel changes in the protein levels; α2 and α4 protein levels did not change after CIE. Both treatments did not alter β2 and β3 mRNA levels, but they increased β2/3 protein levels. The γ2 subunit mRNA levels decreased with both treatments, but protein levels did not change. Most of the changes returned to control levels after withdrawal, except for the γ2 subunit protein, which was lower than controls. In the case of NMDAR subunit, both treatments greatly increased the levels of NR2B mRNA, but barely altered NR1 mRNA and polypeptide levels. CIE treatment caused a relatively higher increase in NR2B protein, and this was the only sustained increase after long-term withdrawal. Taken together, our results show that CIE regimen has less pronounced effects on GABAA receptor expression, but increases NR2B expression more dramatically than CE treatment in cultured cortical neurons. These differential effects on subunit expression may result in altered receptor structure and function as a result of ethanol exposure.
AB - We examined the mRNA and protein levels of GABAA and NMDA receptor (NMDAR) subunits in cultured mouse cortical neurons following exposure to chronic ethanol (CE) or chronic intermittent ethanol (CIE), and after 5 days of withdrawal. With respect to GABAA receptor mRNA, both treatments decreased the levels of α1 and α2 subunits, and increased the level of α4. However, only CE treatment caused parallel changes in the protein levels; α2 and α4 protein levels did not change after CIE. Both treatments did not alter β2 and β3 mRNA levels, but they increased β2/3 protein levels. The γ2 subunit mRNA levels decreased with both treatments, but protein levels did not change. Most of the changes returned to control levels after withdrawal, except for the γ2 subunit protein, which was lower than controls. In the case of NMDAR subunit, both treatments greatly increased the levels of NR2B mRNA, but barely altered NR1 mRNA and polypeptide levels. CIE treatment caused a relatively higher increase in NR2B protein, and this was the only sustained increase after long-term withdrawal. Taken together, our results show that CIE regimen has less pronounced effects on GABAA receptor expression, but increases NR2B expression more dramatically than CE treatment in cultured cortical neurons. These differential effects on subunit expression may result in altered receptor structure and function as a result of ethanol exposure.
KW - Chronic ethanol
KW - Chronic intermittent ethanol
KW - GABA receptor
KW - NR1 and NR2B subunits
KW - Neurotransmitters
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U2 - 10.1016/j.alcohol.2006.05.002
DO - 10.1016/j.alcohol.2006.05.002
M3 - Article
C2 - 16839855
AN - SCOPUS:33745698963
VL - 38
SP - 89
EP - 97
JO - Alcohol
JF - Alcohol
SN - 0741-8329
IS - 2
ER -