Liu Jiangping, Schmitt Kathy L, Kharlamov Elena A, Stolarski Carol J, Grayson Dennis R, Kelly Kevin M
Department of Neurology, Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA 15212-4772, USA.
Epilepsy Res. 2002 Dec;52(2):85-95. doi: 10.1016/s0920-1211(02)00194-8.
Photothrombotic brain infarction can result in altered expression of cortical GABA(A) receptors and in epileptic seizures. We sought to determine whether infarct size and/or epileptic seizures resulted in a differential expression of cortical GABA(A) receptor subunit mRNA in adult rats. A reverse transcription-polymerase chain reaction (RT-PCR) was used with internal standards for GABA(A) receptor subunits to quantify alpha(1), beta(1), and gamma(2S) subunit mRNA expression in cortex ipsilateral and contralateral to left cerebral infarcts in small or large infarct/nonepileptic cohorts, a large infarct/epileptic cohort, and a young adult control cohort. Unilateral hemispheric subunit mRNA was pooled for each cohort, quantified, and expressed as mean values+/-S.E.M. In general, the magnitude of mRNA expression (pg/1 microg total RNA) was different for the individual subunits: gamma(2S) (10(4)), alpha(1) (10(2)), and beta(1) (10(1)). Hemispheric subunit mRNA expression for the different cohorts was compared by ANOVA testing, which noted significant differences for the alpha(1) (P<0.001) and beta(1) (P<0.001) subunits in ipsilateral cortex. Bonferroni post-testing for alpha(1) cohorts indicated that mRNA expression for the large infarct/epilepsy cohort (624.2+/-6.8 pg) was greater than all other cohorts (P<0.001); control (162.7+/-32.2 pg). For beta(1) cohorts, there was decreased mRNA expression in the large infarct/nonepileptic cohort (9.2+/-0.8 pg; P<0.01) and the large infarct/epileptic cohort (10.5+/-2.2 pg; P<0.05) compared to control (23.2+/-2.6 pg). Additionally, paired t-tests compared subunit mRNA expression within individual animal cohorts (ipsilateral vs. contralateral) and indicated decreased mRNA expression ipsilaterally for the beta(1) subunit in the small infarct cohort (14.2+/-2.6 vs. 22.9+/-3.0 pg; P=0.0102) and the large infarct/epilepsy cohort (10.5+/-2.3 vs. 18.0+/-3.6 pg; P=0.0462). These findings suggest that large photothrombotic infarcts of the neocortex can result in a long-lasting differential expression of GABA(A) receptor subunit mRNAs in ipsilateral cortex variably associated with the epileptic state.
光血栓性脑梗死可导致皮质GABA(A)受体表达改变及癫痫发作。我们试图确定梗死灶大小和/或癫痫发作是否会导致成年大鼠皮质GABA(A)受体亚基mRNA的差异表达。采用逆转录-聚合酶链反应（RT-PCR）及GABA(A)受体亚基内标，对小梗死/无癫痫组、大梗死/癫痫组和成年对照组长时程左侧脑梗死同侧及对侧皮质中α(1)、β(1)和γ(2S)亚基mRNA表达进行定量。将每组单侧半球亚基mRNA合并、定量，并表示为平均值±标准误。一般来说，各亚基mRNA表达量（pg/1μg总RNA）不同：γ(2S)（10⁴）、α(1)（10²）和β(1)（10¹）。通过方差分析比较不同组的半球亚基mRNA表达，结果显示同侧皮质中α(1)（P<0.001）和β(1)（P<0.001）亚基存在显著差异。α(1)亚基的Bonferroni事后检验表明，大梗死/癫痫组的mRNA表达量（624.2±6.8 pg）高于所有其他组（P<0.001）；对照组为（162.7±32.2 pg）。对于β(1)亚基组，与对照组（23.2±2.6 pg）相比，大梗死/无癫痫组（9.2±0.8 pg；P<0.01）和大梗死/癫痫组（10.5±2.2 pg；P<0.05）的mRNA表达降低。此外，配对t检验比较了个体动物组内（同侧与对侧）的亚基mRNA表达，结果显示小梗死组（14.2±2.6 vs. 22.9±3.0 pg；P=0.0102）和大梗死/癫痫组（10.5±2.3 vs. 18.0±3.6 pg；P=0.0462）同侧β(1)亚基的mRNA表达降低。这些发现表明，新皮质的大型光血栓性梗死可导致同侧皮质中GABA(A)受体亚基mRNA的长期差异表达，且与癫痫状态存在不同程度的关联。
