Excitatory amino acid transporter (EAAT)1 and EAAT2 mRNA levels are altered in the prefrontal cortex of subjects with schizophrenia.

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.

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