Ionotropic glutamate receptor mRNA expression in the human thalamus: absence of change in schizophrenia - PubMed (original) (raw)

Ionotropic glutamate receptor mRNA expression in the human thalamus: absence of change in schizophrenia

Stella Dracheva et al. Brain Res. 2008.

Abstract

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.

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Figures

Figure 1

A) Representative uncoverslipped thionin stained 20 micron coronal frozen section through the middle of the thalamus at the level of the CM. Arrows indicate the internal medullary lamina. Abbreviations: CM centromedian nucleus; f, fasciculus retroflexus ; MDl lateral sector of mediodorsal nucleus; MDm medial sector of medial dorsal nucleus; Pf parafascicular nucleus; VLp ventrolateral posterior nucleus; VP ventral posterior nucleus. B) Same section as in panel A after laser microdissection of the CM. The dots were placed on the glass side of the Leica microdissection slides to delineate the divisions to be dissected (see Experimental Procedures).

Figure 2

Gene expression analysis by thalamic nucleus. mRNA expression levels of NMDA, AMPA, and kainate receptor subunits for the entire cohort are shown.

Figure 3

Gene expression analysis by thalamic nucleus and diagnosis. mRNA expression is shown for (A) NMDA (B) AMPA, and (C) kainate receptor subunits. The expression levels for all glutamate receptor subunits detected varied significantly across nuclei. There were no differences between the diagnoses. Histograms represent means and SEMs. For each gene, histograms that do not share the same symbol (a,b,or c) represent means that differ statistically (p<0.005) after Bonferroni correction. ns, not significant.

Figure 3

Figure 4

Graphic summary of the relative levels of iGluR and PSD95 gene expression in the 5 thalamic nuclei studied. Displayed is the summary of results shown in Figures 2 and 3. RED indicates high expression, BLUE moderate expression, GREEN low expression

References

1. Akbarian S, Sucher NJ, Bradley D, Tafazzoli A, Trinh D, Hetrick WP, Potkin SG, Sandman CA, Bunney WE, Jr, Jones EG. Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics, J Neurosci. 1996;16:19–30. -PMC -PubMed
1. Alt A, Weiss B, Ogden AM, Knauss JL, Oler J, Ho K, Large TH, Bleakman D. Pharmacological characterization of glutamatergic agonists and antagonists at recombinant human homomeric and heteromeric kainate receptors in vitro, Neuropharmacology. 2004;46:793–806. -PubMed
1. Andreasen NC. Schizophrenia: the fundamental questions. Brain Res Brain Res Rev. 2000;31:106–112. -PubMed
1. Benes FM, Vincent SL, Todtenkopf M. The density of pyramidal and nonpyramidal neurons in anterior cingulate cortex of schizophrenic and bipolar subjects, Biol Psychiatry. 2001;50:395–406. -PubMed
1. Beneyto M, Meador-Woodruff JH. Expression of transcripts encoding AMPA receptor subunits and associated postsynaptic proteins in the macaque brain. J Comp Neurol. 2004;468:530–554. -PubMed

Ionotropic glutamate receptor mRNA expression in the human thalamus: absence of change in schizophrenia - PubMed (original) (raw)