Comparison of chronic ethanol and chronic intermittent ethanol treatments on the expression of GABA(A) and NMDA receptor subunits.

Comparison of chronic ethanol and chronic intermittent ethanol treatments on the expression of GABA(A) and NMDA receptor subunits.
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慢性乙醇和慢性间歇乙醇治疗对GABA(A)和NMDA受体亚基表达的比较。

DOI:
10.1016/j.alcohol.2006.05.002
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发表时间:
2006
期刊:
Alcohol (Fayetteville, N.Y.)
影响因子:
--
通讯作者:
Ticku,MaharajK
Ticku,MaharajK
中科院分区:
--
文献类型:
--
作者:
SheelaRani,CS;Ticku,MaharajK

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我们检测了慢性乙醇(CE)或慢性间歇乙醇(CIE)以及停药5天后培养的小鼠皮质神经元GABAA和NMDAR亚单位的mRNA和蛋白水平。在GABAA受体基因表达方面,两种处理均使α-1和α-2亚单位表达降低,α-4表达增加,但仅CE处理引起的蛋白表达水平变化不明显,α-2和α-4蛋白表达水平无明显变化。两种处理均不改变β-2和β-3m RNA水平,但提高了β-2/3蛋白水平。γ-2亚单位基因表达水平随处理时间延长而降低,但蛋白水平无明显变化。停药后,除γ2亚单位蛋白低于对照组外,其余变化均恢复到对照组水平。在NMDAR亚单位的情况下,两种处理都显著提高了NR2B的mRNA水平,但几乎没有改变NR1mRNA和多肽的水平。CIE治疗引起NR2B蛋白相对较高的增加,这是长期停药后唯一一次持续增加。综上所述,我们的结果表明,CIE方案对培养的皮质神经元GABAA受体表达的影响不明显,但比CE处理更显著地增加了NR2B的表达。这些对亚单位表达的不同影响可能会导致酒精暴露导致受体结构和功能的改变。
We examined the mRNA and protein levels of GABAAand 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 GABAAreceptor 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 GABAAreceptor 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.
慢性 GABA 暴露会下调培养的大脑皮层神经元中的 GABA-苯二氮卓受体-离子载体复合物。
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