Archival ReportIncreased SNARE Protein-Protein Interactions in Orbitofrontal and Anterior Cingulate Cortices in Schizophrenia
Section snippets
Human Postmortem Brains
For the main prospective study (cohort 1), samples were obtained from the Macedonian/New York State Psychiatric Institute Brain Collection (36). Demographic and toxicological data of subjects with schizophrenia (n = 15) and matched control subjects (n = 13) are summarized in Tables S1 and S2 in Supplement 1. Postmortem intervals (PMI) for all samples were relatively short compared with other available human cohorts (51), with control subjects (mean 16.6 ± SD 7.1 hours) having slightly but
Inspection of Datasets and Relationships with Potentially Confounding Variables
All data series obtained in the neurochemical assessments were normally distributed. Except for PMI, no relevant associations were found between potentially confounding variables (age at death; gender; brain pH; sample storage time; presence of antipsychotics, benzodiazepines, and/or ethanol; and/or smoking habit) and the neurochemical findings. Since schizophrenia and control subjects within cohort 1 differed statistically in mean PMI (Table S1 in Supplement 1), multiple approaches were used
Discussion
The present study explored the diversity of interactions of SNARE proteins (Stx1, SNAP25, and VAMP) and relevant presynaptic binding partners (Munc18-1, Cplx1/2, Stg) with two different immunoassay strategies (co-IP and BN-PAGE). Schizophrenia was associated with greater OFC and ACC SNARE complex formation, without alteration in protein expression levels. Greater Cplx1 and/or Munc18-1 binding affinity may underlie the aberrant SNARE complex formation in schizophrenia.
Native gels were used for
Acknowledgments and Disclosures
The study was supported by the Canadian Institutes of Health Research (MT-14037, MOP-81112) and the Michael Smith Foundation for Health Research, the National Institute of Mental Health (MH60877, MH64168, MH62185, MH45212, MH64673), National Alliance for Research on Schizophrenia and Depression, and the Lieber Center for Schizophrenia Research. AR-M is a postdoctoral fellow supported by Michael Smith Foundation for Health Research and BC Schizophrenia Society Foundation.
We thank Hong-Ying Li
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