Increased Density of Glutamate-immunoreactive Vertical Processes in Superficial Laminae in Cingulate Cortex of Schizophrenic Brain

Abstract

Recent postmortem investigations have suggested that schizophrenia may involve a defect in associative information processing in the upper layers of limbic cortex. One of these studies reported that vertical processes visualized with antibodies against the neurofilament 200K subunit (NFP-200K) of the axon cytoskeleton were increased in density in layer II and upper portions of layer IIIa of the cingulate region of schizophrenic individuals. Based on this latter finding, it was hypothesized that there may be a superbundance of associative afferents to this region. To explore this possibility further, an immunoperoxidase localization of the amino acid glutamate has been employed to visualize vertical fibers in layers II and IIIa of postmortem anterior cingulate cortex in both normal controls (n = 15) and schizophrenics (n = 17). Vertical fibers were distinguished according to small or large calibers and were differentially counted with a blind computer-assisted technique. The schizophrenic group showed a markedly higher density (77.8%) of small-caliber glutamate-immunoreactive vertical fibers when compared to controls; the density of large-caliber vertical fibers also showed a similar, though smaller (30.2%), increase in the schizophrenic group. There were no differences in the density of either small- or large-caliber processes in prefrontal cortex of the two groups. The effects of age, postmortem interval, fixation, and neuroleptic exposure do not account for the differences between the normal and schizophrenic subjects. Taking together their small caliber, vertical orientation, localization in superficial layers, and marked glutamate immunoreactivity, it seems plausible that the fibers showing an increased density in schizophrenics may be glutamatergic afferents, possibly ones that are associative in nature.(ABSTRACT TRUNCATED AT 250 WORDS)

Schizophrenia and viral infection during neurodevelopment: a focus on mechanisms

“…127 This decrement, however, may not be uniformly expressed because the opposite is suggested by increased levels of glutamate reuptake sites in frontal and cingulate cortex, 124,128 and an elevated density of glutamatergic fibers in the anterior cingulate. 129 These discrepant neurochemical findings have not been clarified by analysis of excitatory amino acid (EAA) receptors in various brain regions thought to be affected in schizophrenia. Despite technical advances in analyzing NMDA and non-NMDA receptors, and the recent discovery of G-protein-linked metabotropic glutamate receptors, a consistent pattern of EAA receptor abnormalities has not been discernible in the disease.…”

A proteome analysis of the anterior cingulate cortex gray matter in schizophrenia

“…Within the ACC there is an observed gray matter volume reduction 3 and accordingly, reduced laminar thickness, 7 a reduction of pyramidal neurons in the deeper lamina 8,9 and smaller pyramidal neuron size. 7,8 In layer II of the ACC vertical fibres are increased 10 and small neurons decreased. 9 These structural and morphological changes within subsets of schizophrenia patients point to a dysfunction within the ACC in the disease pathology.…”

Does Ketamine-Mediated N-methyl-D-aspartate Receptor Antagonism Cause Schizophrenia-like Oculomotor Abnormalities?

“…Involvement of sigma receptors in the action of ketamine is unlikely, because the behavioral effects of ketamine correlate with NMDA, but not sigma, receptor binding affinity (Ginski and Witkin 1994). The presence of glutamatergically mediated psychotomimetic effects of ketamine is also congruent with histological (Benes et al 1991;Benes et al 1992;Benes 1995;Simpson et al 1991;Ishimaru et al 1994;Akbarian et al 1996) and neuroimaging (Bartha et al 1997) evidence for glutamatergic abnormalities in schizophrenia (see also Olney and Farber 1995).…”