Matthews D B, Devaud L L, Fritschy J M, Sieghart W, Morrow A L
Bowles Center for Alcohol Studies, Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill 27599-7178, USA.
J Neurochem. 1998 Mar;70(3):1160-6. doi: 10.1046/j.1471-4159.1998.70031160.x.
Previous research has shown that chronic ethanol consumption dramatically alters GABA(A) receptor alpha1 and alpha4 subunit gene expression in the cerebral cortex and GABA(A) receptor alpha1 and alpha6 subunit gene expression in the cerebellum. However, it is not yet known if chronic ethanol consumption produces similar alterations in GABA(A) receptor gene expression in other brain regions. One brain region of interest is the hippocampus because it has recently been shown that a subset of GABA(A) receptors in the hippocampus is responsive to pharmacologically relevant concentrations of ethanol. Therefore, we directly compared the effects of chronic ethanol consumption on GABA(A) receptor subunit gene expression in the hippocampus and cerebral cortex. Furthermore, we investigated whether the duration of ethanol consumption (14 or 40 days) would influence regulation of GABA(A) receptor gene expression in these two brain regions. Chronic ethanol consumption produced a significant increase in the level of GABA(A) receptor alpha4 subunit peptide in the hippocampus following 40 days but not 14 days. The relative expression of hippocampal GABA(A) receptor alpha1, alpha2, alpha3, beta(2/3), or gamma2 was not altered by either period of chronic ethanol exposure. In marked contrast, chronic ethanol consumption for 40 days significantly increased the relative expression of cerebral cortical GABA(A) receptor alpha4 subunits and significantly decreased the relative expression of cerebral cortical GABA(A) receptor alpha1 subunits. This finding is consistent with previous results following 14 days of chronic ethanol consumption. Hence, chronic ethanol consumption alters GABA(A) receptor gene expression in the hippocampus but in a different manner from that in either the cerebral cortex or the cerebellum. Furthermore, these alterations are dependent on the duration of ethanol exposure.
先前的研究表明，长期摄入乙醇会显著改变大脑皮层中GABA(A)受体α1和α4亚基的基因表达，以及小脑GABA(A)受体α1和α6亚基的基因表达。然而，长期摄入乙醇是否会在其他脑区产生类似的GABA(A)受体基因表达变化尚不清楚。一个值得关注的脑区是海马体，因为最近有研究表明，海马体中的一部分GABA(A)受体对药理学相关浓度的乙醇有反应。因此，我们直接比较了长期摄入乙醇对海马体和大脑皮层中GABA(A)受体亚基基因表达的影响。此外，我们还研究了乙醇摄入的持续时间（14天或40天）是否会影响这两个脑区中GABA(A)受体基因表达的调控。长期摄入乙醇40天后，海马体中GABA(A)受体α4亚基肽水平显著升高，但14天后未出现这种情况。长期乙醇暴露的两个阶段均未改变海马体中GABA(A)受体α1、α2、α3、β(2/3)或γ2的相对表达。与之形成鲜明对比的是，长期摄入乙醇40天显著增加了大脑皮层中GABA(A)受体α4亚基的相对表达，并显著降低了大脑皮层中GABA(A)受体α1亚基的相对表达。这一发现与长期摄入乙醇14天后的先前结果一致。因此，长期摄入乙醇会改变海马体中GABA(A)受体基因的表达，但方式与大脑皮层或小脑不同。此外，这些变化取决于乙醇暴露的持续时间。
