Differential alterations of kainate receptor subunits in inhibitory interneurons in the anterior cingulate cortex in schizophrenia and bipolar disorder.
The aim of this study was to examine whether glutamatergic inputs onto GABA interneurons via the kainate receptor in the anterior cingulate cortex may be altered in schizophrenia and bipolar disorder. Hence, in a cohort of 60 post-mortem human brains from schizophrenia, bipolar disorder, and normal control subjects, we simultaneously labeled the mRNA for the GluR5 or GluR6 subunit of the kainate receptor with [(35)S] and the mRNA for the 67 kD isoform of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD)(67) with digoxigenin using an immunoperoxidase method. The density of the GAD(67) mRNA-containing neurons that co-expressed GluR5 mRNA was decreased by 43% and 40% in layer 2 of the anterior cingulate cortex in schizophrenia and bipolar disorder, respectively. In contrast, the density of the GAD(67) mRNA-containing cells that expressed GluR6 mRNA was unaltered in either condition. Furthermore, the amount of GluR5 or GluR6 mRNA in the GAD(67) mRNA-expressing cells that contained a detectable level of these transcripts was also unchanged. Finally, the density of cells that did not contain GAD(67) mRNA, which presumably included all pyramidal neurons, but expressed the mRNA for the GluR5 or GluR6 subunit was not altered. Thus, glutamatergic modulation of inhibitory interneurons, but not pyramidal neurons, via kainate receptors containing the GluR5 subunit appears to be selectively altered in the anterior cingulate cortex in schizophrenia and bipolar disorder.
Woo
Tsung-Ung W
TU
Program in Structural and Molecular Neuroscience, McLean Hospital, Belmont, MA 02478, USA.
Shrestha
Kevin
K
Amstrong
Christopher
C
Minns
Martin M
MM
Walsh
John P
JP
Benes
Francine M
FM
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001706:Biopsy; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002648:Child; D005260:Female; D007839:Functional Laterality; D006179:Gyrus Cinguli / Q000033:anatomy & histology / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D021122:Protein Subunits / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
D014150:Antipsychotic Agents; D021122:Protein Subunits; D018092:Kainic Acid Receptors
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