Excitatory amino acid transporter (EAAT)1 and EAAT2 mediate glutamatergic neurotransmission and prevent excitotoxicity through binding and transportation of glutamate into glia. These EAATs may be regulated by metabotropic glutamate receptor 5 (mGluR5), which is also expressed by glia. Whilst we have data from an Affymetrix™ Human Exon 1.0 ST Array showing higher levels of EAAT1 mRNA (+36%) in Brodmann's are (BA)9 of subjects with schizophrenia, there is evidence that EAAT1 and EAAT2, as well as mGluR5 levels, are altered in the cortex of subjects with the disorder. Hence, we measured mRNA levels of these genes in other cortical regions in subjects with that disorder. EAAT1, EAAT2 and mGluR5 mRNA were measured, in triplicate, using Quantitative PCR in BA10 and BA46 from subjects with schizophrenia (n = 20) and age and sex matched controls (n = 18). Levels of mRNA were normalised to the geometric mean of two reference genes, transcription factor B1, mitochondrial (TFB1M) and S-phase kinase-associated protein 1A (SKP1A), for which mRNA did not vary between diagnostic groups in either region. Normalised levels of EAAT1 and EAAT2 mRNA were significantly higher in BA10 (EAAT1: U = 58, p = 0.0002; EAAT2 U = 70, p = 0.0009), but not BA46 (EAAT1: U = 122, p = 0.09; EAAT2: U = 136, p = 0.21), from subjects with schizophrenia compared to controls. mGluR5 levels in BA10 (U = 173, p=0.85) and BA46 (U = 178, p = 0.96) did not vary by cohort. Our data suggests that region-specific increases in cortical EAAT1 and EAAT2 mRNA are involved in schizophrenia pathophysiology and that disrupted glutamate uptake in schizophrenia may be of particular significance in BA10.

中文翻译：

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精神分裂症患者前额叶皮层的兴奋性氨基酸转运蛋白 (EAAT)1 和 EAAT2 mRNA 水平发生改变。

兴奋性氨基酸转运蛋白 (EAAT)1 和 EAAT2 介导谷氨酸能神经传递，并通过谷氨酸结合和转运到胶质细胞中来防止兴奋性毒性。这些 EAAT 可能受代谢型谷氨酸受体 5 (mGluR5) 的调节，mGluR5 也由神经胶质细胞表达。虽然我们有来自 Affymetrix™ 人外显子 1.0 ST 阵列的数据显示 Brodmann 的 EAAT1 mRNA 水平较高（+36%），但有证据表明 EAAT1 和 EAAT2 以及 mGluR5 水平，在患有该疾病的受试者的皮层中发生改变。因此，我们在患有该疾病的受试者的其他皮质区域测量了这些基因的 mRNA 水平。一式三份测量 EAAT1、EAAT2 和 mGluR5 mRNA，使用来自精神分裂症（n = 20）和年龄和性别匹配对照（n = 18）的受试者的 BA10 和 BA46 中的定量 PCR。将 mRNA 水平标准化为两个参考基因的几何平均值，即转录因子 B1、线粒体 (TFB1M) 和 S 期激酶相关蛋白 1A (SKP1A)，其 mRNA 在任一区域的诊断组之间均无差异。EAAT1 和 EAAT2 mRNA 的标准化水平在 BA10 中显着更高（EAAT1：U = 58，p = 0.0002；EAAT2 U = 70，p = 0.0009），但不是 BA46（EAAT1：U = 122，p = 0.09；EAAT2：U = 136, p = 0.21)，来自与对照组相比的精神分裂症受试者。BA10 (U = 173, p = 0.85) 和 BA46 (U = 178, p = 0.96) 中的 mGluR5 水平没有因队列而异。