Ionotropic glutamate receptor mRNA expression in the human thalamus: absence of change in schizophrenia.
Abnormalities in glutamate neurotransmission are thought to be among the major contributing factors to the pathophysiology of schizophrenia. Although schizophrenia has been regarded mostly as a disorder of higher cortical function, the cortex and thalamus work as a functional unit. Existing data regarding alterations of glutamate receptor subunit expression in the thalamus in schizophrenia remain equivocal. This postmortem study examined mRNA expression of ionotropic glutamate receptor (iGluR) subunits and PSD95 in 5 precisely defined and dissected thalamic subdivisions (medial and lateral sectors of the mediodorsal nucleus; and the ventral lateral posterior, ventral posterior, and centromedian nuclei) of persons with schizophrenia and matched controls using quantitative PCR with normalization to multiple endogenous controls. Among 15 genes examined (NR1 and NR2A-D subunits of the NMDA receptor; GluR1-4 subunits of the AMPA receptor; GluR5-7 and KA1-2 subunits of the kainate receptor; PSD95), all but two (GluR4 and KA1) were expressed at quantifiable levels. Differences in iGluR gene expression were seen between different thalamic nuclei but not between diagnostic groups. The relative abundance of transcripts was: NR1>>NR2A>NR2B>NR2D>NR2C for NMDA, GluR2>GluR1>GluR3 for AMPA, and KA2>GluR5>GluR7>GluR6 for kainate receptors. The expression of PSD95 correlated with the expression of NR1, NR2A, NR2B, NR2D and GluR6 in all nuclei. These results provide detailed and quantitative information on iGluR subunit expression in multiple nuclei of the human thalamus but suggest that alterations in their expression are not a prominent feature of schizophrenia.
Dracheva
Stella
S
Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY, USA.
Byne
William
W
Chin
Benjamin
B
Haroutunian
Vahram
V
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D008297:Male; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000378:metabolism*; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D017470:Receptors, Glutamate / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000473:pathology*; D013788:Thalamus / Q000378:metabolism*
D012333:RNA, Messenger; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; C104724:glutamate receptor ionotropic, AMPA 4