Isotype-Specific G Protein Abnormalities in the Left Superior Temporal Cortex and Limbic Structures of Patients with Chronic Schizophrenia

Background:The potential role of signal transducing guanine nucleotide-binding regulatory protein (G protein) in schizophrenia is largely unknown. Methods:We immunoquantified isotypes of G protein using specific antisera against α and β subunits of G protein in the superior temporal, prefrontal, and entorhinal cortices as well as the nucleus accumbens and amygdala of postmortem brains from 19 schizophrenic and 28 control subjects. Results:In the left hemisphere of schizophrenics, the amount of Giα, Goα, and Gqα but not that of Gsα or Gβ decreased in the superior temporal cortex by 27%, 27%, and 16%, respectively, as compared with the values in ipsilateral controls; the amount of any G protein isotype in the prefrontal and entorhinal cortices was not changed. In the nucleus accumbens and amygdala, the paranoid type schizophrenics showed a smaller amount of Giα and Goα than the disorganized type schizophrenics. In the right superior temporal cortex, the isotype amount did not differ between the schizophrenic and control groups. Conclusions:The decreased Gqα immunoreactivity in the schizophrenic left superior temporal cortex may reflect the down-regulation of Gqα, resulting from chronic stimulation of Gqα-coupled receptors, while the decreased Giα and Goα in the nucleus accumbens and amygdala of paranoid type schizophrenics may be related to the dopaminergic hyperactivity via dopamine D2 receptors.