Excitatory Amino Acid Transporter Expression and Regulation in Prefrontal Cortex in Schizophrenia.

[摘要] The glutamate hypothesis of schizophrenia, which is based primarily on NMDA receptor dysfunction, can be expanded to include additional components of the glutamate synapse including the excitatory amino acid transporters (EAATs) which buffer and transport synaptic glutamate.I studied multiple levels of expression and regulation of the EAATs in postmortem prefrontal cortex from patients with schizophrenia and comparison subjects.I used in situ hybridization, Western Blot analysis, enzymatic deglycosylation, and QPCR to study EAAT expression and regulation in the prefrontal cortex in schizophrenia.I found decreased EAAT1 protein expression, and found several factors that indicate decreased localization of EAATs at the synapse including decreased glycosylation of EAAT1 and EAAT2, increased expression of the ER retention variant EAAT2Δ9, and increased expression of molecules that retain EAATs in the ER, GPS1 and JWA.These data suggest decreased overall EAAT expression, and abnormal localization of EAATs that are expressed.Therefore, there are likely fewer EAATs expressed at the cell surface, and thus a decrease in the capacity for glutamate buffering and transport. These data demonstrate novel sites of disruption in the glutamate synapse in schizophrenia.This work could therefore provide alternative targets for developing new treatments for schizophrenia.

[发布机构] University of Michigan

[效力级别] Glutamate Transporter

[关键词] Schizophrenia;Glutamate Transporter;Excitatory Amino Acid Transporter;EAAT;Prefrontal Cortex;Molecular;Cellular and Developmental Biology;Science;Neuroscience