Altered Vesicular Glutamate Transporter Expression in the Anterior Cingulate Cortex in Schizophrenia

Abstract

Background-Schizophrenia is a chronic, severe mental illness with profound emotional and economic burdens for those afflicted and their families. An increasing number of studies have found that schizophrenia is marked by dysregulation of glutamatergic neurotransmission. While numerous studies have found alterations of postsynaptic molecules in schizophrenia, a growing body of evidence implicates presynaptic factors. Vesicular glutamate transporters (VGLUTs) have been identified and are known to package glutamate into vesicles in the presynaptic terminal for subsequent release into the synaptic cleft. Recent studies have shown that VGLUTs regulate synaptic activity via the amount of glutamate released. Accordingly, we hypothesized that VGLUTs are altered in schizophrenia, contributing to dysfunction of presynaptic activity.

Abnormal Activity of the MAPK- and cAMP-Associated Signaling Pathways in Frontal Cortical Areas in Postmortem Brain in Schizophrenia

“…Regional differences in molecular abnormalities in schizophrenia are consistently reported in the literature (Katsel et al, 2005a, b;Kristiansen et al, 2006Kristiansen et al, , 2010Oni-Orisan et al, 2008), and although the sets of changes we found differed by cortical region, each set is functionally similar, resulting in decreased signal integration in both regions. This differential expression pattern may be inherent to the physiological circuits and inputs for each region.…”

“…Neuropathological examination revealed no neurodegenerative diseases including Alzheimer's disease in any subjects. Next of kin consent was obtained for each patient (Bauer et al, 2008(Bauer et al, , 2009(Bauer et al, , 2010Funk et al, 2009;Hammond et al, 2010;Oni-Orisan et al, 2008). Schizophrenia and comparison groups were matched for sex, age, pH, and PMI (Table 1).…”

“…The assessment included the CERAD battery, the Clinical Dementia Rating Scale, and the Positive and Negative Syndrome Scale (Powchik et al, 1998). Comparison subjects were also evaluated for dementia and neurodegenerative diseases as well as any history of drug and alcohol abuse (Oni-Orisan et al, 2008). Detailed tables of comparison and schizophrenia subjects (Supplementary Tables 1 and 2) are provided as a comprehensive list of specific demographics for each group.…”

Synaptic Proteins in the Postmortem Anterior Cingulate Cortex in Schizophrenia: Relationship to Treatment and Treatment Response

“…This discrepancy may be due to several factors. Our cohort was younger, racially mixed, and the tissue sample area may have come from different areas of the ACC than those used in the study of Oni-Orisan et al (2008). Glutamatergic terminals from cortex or thalamus contain vGLUT1 and vGLUT2, respectively (Fremeau et al, 2004), and are used to label the respective connections.…”

“…Postmortem studies of the ACC in SZ indicate numerous abnormalities (Todtenkopf et al, 2005;Oni-Orisan et al, 2008; for review see Fornito et al, 2009;Kraguljac et al, 2012a,b). Neurobiological differences between treatment response and treatment resistance in SZ are rarely studied in postmortem tissue, but provide a strategy for trying to link psychosis with particular neuropathology .…”