Excitatory Amino Acid Transporter Expression and Regulation in Schizophrenia

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DESCRIPTION (provided by applicant): The excitatory amino acid transporters (EAATs) are a family of molecules responsible for synaptic glutamate reuptake. Expression and regulation of these transporters facilitates clearance of glutamate from the synapse and plays a pivotal role in long-term potentiation and synaptic plasticity. Compelling evidence has implicated cortical abnormalities of glutamate transmission in schizophrenia, but the precise role of the EAATs in schizophrenia remains unknown. It is hypothesized that expression and regulation of EAATs are altered in the prefrontal and anterior cingulate cortices in schizophrenia in a pattern consistent with increased glutamate reuptake. In postmortem tissue from patients with schizophrenia and control subjects, cell level gene expression will be measured using laser capture microscopy and quantitative PCR, post translational modification will be studied using enzymatic deglycoslation and Western blot analysis, and interaction between the transporters and a set of proteins that modulate transporter activity will be measured using co-immunoprecipitation. Schizophrenia affects 1% of the population worldwide and the cost to the U.S. in 2002 was estimated to be $62.7 billion. This research will lead to significant advances in our understanding of how glutamate reuptake may be altered in schizophrenia. Defining the specific abnormalities in glutamatergic neurotransmission may be used to target more effective diagnostic and treatment strategies.