mRNA expression of AMPA receptors and AMPA receptor binding proteins in the cerebral cortex of elderly schizophrenics.
L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate the majority of the fast excitatory transmission in the CNS. To determine whether gene expression of AMPARs and/or AMPAR binding proteins, which control response/sensitivity of AMPAR-bearing neurons to glutamate, are altered in schizophrenia, mRNA expression and abundance of AMPAR subunits (GluR1-4) and several AMPAR binding proteins (SAP97, PICK1, GRIP, ABP) were measured in the dorsolateral prefrontal cortex (DLPFC) and the occipital cortex of elderly schizophrenia patients (n = 36) and matched normal controls (n = 26) by quantitative real-time PCR. The mRNA expression of GluR1, GluR4, and GRIP in the DLPFC and expression of the GluR4, GRIP, and ABP in the occipital cortex were significantly elevated in schizophrenics. GluR1 and ABP mRNA expression in the occipital cortex and GluR2, GluR3, SAP97, and PICK1 expression in either cortical area were not significantly altered. The data also demonstrated significant differences in the abundances of mRNAs encoding GluR1-4 subunits (GluR2 > GluR3 > GluR1 > GluR4) and of AMPAR binding proteins (SAP97 > PICK1 > GRIP > ABP) in both diagnostic groups. GluR2 (58-64%) and GluR3 (24-29%) were the major components of the AMPAR mRNA in both cortical areas, implying that the major AMPAR complexes in the human cortex are probably those containing GluR2 and GluR3 subunits. Small but significant differences in the amounts of GluR2, GluR3, and GRIP mRNAs were detected between the two cortical areas: more GluR3 and GRIP but less GluR2 were detected in the DLPFC than in the occipital cortex.
Dracheva
Stella
S
Department of Psychiatry, The Mount Sinai School of Medicine, New York, New York, USA.
McGurk
Susan R
SR
Haroutunian
Vahram
V
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D000074288:Discs Large Homolog 1 Protein; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000378:metabolism; D018091:Receptors, AMPA / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C498297:PICk1 protein, human; D012333:RNA, Messenger; D018091:Receptors, AMPA