Abnormal expression of glutamate transporter and transporter interacting molecules in prefrontal cortex in elderly patients with schizophrenia.
Glutamate cycling is critically important for neurotransmission, and may be altered in schizophrenia. The excitatory amino acid transporters (EAATs) facilitate the reuptake of glutamate from the synaptic cleft and have a key role in glutamate cycling. We hypothesized that expression of the EAATs and the EAAT regulating proteins ARHGEF11, JWA, G-protein suppressor pathway 1 (GPS1), and KIAA0302 are altered in the brain in schizophrenia. To test this, we measured expression of EAAT1, EAAT2, EAAT3, and EAAT interacting proteins in postmortem tissue from the dorsolateral prefrontal and anterior cingulate cortex of patients with schizophrenia and a comparison group using in situ hybridization and Western blot analysis. We found increased EAAT1 transcripts and decreased protein expression, increased EAAT3 transcripts and protein, and elevated protein expression of both GPS1 and KIAA0302 protein. We did not find any changes in expression of EAAT2. These data indicate that proteins involved in glutamate reuptake and cycling are altered in the cortex in schizophrenia, and may provide potential targets for future treatment strategies.
Bauer
Deborah
D
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294-0017, United States. debbauer@uab.edu
Gupta
Daya
D
Harotunian
Vahram
V
Meador-Woodruff
James H
JH
McCullumsmith
Robert E
RE
D000368:Aged; D000369:Aged, 80 and over; D027322:Amino Acid Transport System X-AG / Q000235:genetics* / Q000378:metabolism*; D015153:Blotting, Western; D002450:Cell Communication / Q000502:physiology*; D016373:DNA, Antisense; D005260:Female; D020869:Gene Expression Profiling; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism*
D027322:Amino Acid Transport System X-AG; D016373:DNA, Antisense; D050491:Glutamate Plasma Membrane Transport Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger