Expression of excitatory amino acid transporter transcripts in the thalamus of subjects with schizophrenia.
OBJECTIVE
Recent investigations of schizophrenia have targeted glutamatergic neurotransmission, since phencyclidine, an N-methyl-D-aspartate (NMDA) receptor antagonist, can induce schizophreniform psychosis. The authors previously reported alterations in thalamic NMDA receptor subunit expression in schizophrenia, consistent with the hypothesis that thalamic glutamatergic hypofunction may contribute to the pathophysiology of this illness. In this study they generalized this hypothesis to include other molecules of the glutamate synapse, specifically excitatory amino acid transporters (EAATs), whose normal expression and regulation in the thalamus may also be disrupted in subjects with schizophrenia.


METHODS
In situ hybridization with riboprobes specific for the human excitatory amino acid transporter transcripts EAAT1, EAAT2, and EAAT3 was performed in discrete thalamic nuclei in persons with schizophrenia and comparison subjects.


RESULTS
Higher expressions of transcripts encoding EAAT1 and EAAT2, but not EAAT3, were detected in the thalamus of subjects with schizophrenia.


CONCLUSIONS
These findings support the hypothesis of glutamatergic dysfunction in schizophrenia and suggest that molecules other than glutamate receptors are abnormally expressed in glutamatergic synapses in this illness.
Smith
R E
RE
Department of Psychiatry/Mental Health Research Institute, University of Michigan Medical School, Ann Arbor 48109-0720, USA. smithrob@umich.edu
Haroutunian
V
V
Davis
K L
KL
Meador-Woodruff
J H
JH
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000368:Aged; D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D005260:Female; D050491:Glutamate Plasma Membrane Transport Proteins; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D027981:Symporters; D013787:Thalamic Nuclei / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism*; D014158:Transcription, Genetic
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; C096392:Grin3a protein, rat; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C493400:SLC1A1 protein, human; C493397:SLC1A2 protein, human; C493394:SLC1A3 protein, human; D027981:Symporters