Cingulate cortex presynaptic proteins in schizophrenia

The cingulate cortex shows histological changes in schizophrenia consistent with abnormal development, and possibly associated with synaptic changes. A panel of monoclonal antibodies was used to investigate three distinct presynaptic proteins in cingulate cortex with enzyme linked immunoadsorbent assays (ELISA) and immunoblotting of frozen tissue homogenates, and immunocytochemistry of formalin fixed specimens. The sample comprised 24 controls (mean age 47 yr) and 18 cases of schizophrenia (mean age 49 yr). Overall, increased presynaptic proteins were detected in schizophrenia using a quantitative ELISA (MANOVA diagnosis F=5.27, p=.004). Follow up analysis of each antibody indicated antibody SP6 detected increased synaptic immunoreactivity in schizophrenia (F=9.43, p=.004, controlled for age and postmortem interval). Characterization studies using immunoblotting and fusion proteins indicated the antigen detected was syntaxin, a presynaptic membrane protein. Antibody SP4 (reactive with synaptophysin), and SP12 (reactive with SNAP-25) did not detect significant differences between schizophrenic and control cingulate. Immunoblotting indicated syntaxin, synaptophysin and SNAP-25 had the expected molecular weights in schizophrenia. Double immunostaining studies with confocal microscopy indicated syntaxin and synaptophysin immunoreactivities were not completely overlapping. Elevated levels of a cingulate cortex presynaptic marker in schizophrenia may indicate developmental abnormalities in this region, as synaptic terminals are at higher than adult levels during childhood.