Comparative analysis of group II metabotropic glutamate receptor immunoreactivity in Brodmann's area 46 of the dorsolateral prefrontal cortex from patients with schizophrenia and normal subjects

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Abstract
Glutamate is the primary excitatory neurotransmitter in the mammalian central nervous system, and a key neurotransmitter in prefrontal cortical function. Converging lines of evidence implicate prefrontal cortical dysfunction in the neurobiology of schizophrenia. Thus, aberrant glutamate neurotransmission may underlie schizophrenia and other complex disorders of behavior. Group II metabotropic receptors (mGluRs) are important modulators of glutamatergic and non-glutamatergic neurotransmission. Moreover, in an animal model, an agonist for group II mGluRs has been shown to reverse the behavioral, locomotor, and cognitive effects of the psychotomimetic drug phencyclidine. Accordingly, group II mGluRs constitute attractive targets for the pharmacotherapeutics and study of schizophrenia. Using immunocytochemistry and Western immunoblotting, we compared the localization and levels of group II mGluRs in Brodmann's area 46 of the dorsolateral prefrontal cortex from patients with schizophrenia and normal subjects. Consistent with previous reports, we found that immunolabeling of group II mGluRs is prominent in Brodmann's area 46. The majority of labeling was present on axon terminals distributed in a lamina-specific fashion. No apparent difference in the cellular localization or laminar distribution of immunoreactive group II mGluRs was noted between the two diagnostic groups. Similarly, the levels of receptor immunoreactivity determined by quantitative Western immunoblotting were comparable between schizophrenic patients and normal subjects. We conclude that while the function of group II mGluRs in Brodmann's area 46 of dorsolateral prefrontal cortex may be altered in patients with schizophrenia, this is not evident at the level of protein expression using an antibody against mGluR2 and mGluR3.