Increased expression of the astrocytic glutamate transporter GLT-1 in the prefrontal cortex of schizophrenics

MELONE M. and MATUTE C.: co-first author ABSTRACT To verify whether altered glial glutamate uptake contributes to the reduced efficacy of glutamatergic transmission reported in the prefrontal cortex of schizophrenics, we studied the expression of GLT-1, the transporter responsible for most glutamate transport, in autoptic samples of prefrontal cortex using real time quantitative RT-PCR, immunocytochemistry, and functional assays. GLT-1 mRNA levels in medication-free patients were 2.5-fold higher than in controls, whereas they were normal or reduced in patients treated with antipsychotics. We also observed a 4-fold increase in L-[3H]-Glu uptake in Xenopus oocytes injected with mRNA from the prefrontal cortex of a medication-free schizophrenic and a 2-fold increase in GLT-1 protein in the same cortical area of another medication-free patient. Results suggest that GLT-1 mRNA, protein and function are increased in prefrontal cortex of schizophrenics.