title: Quantitative mass spectrometry reveals changes in SNAP-25 isoforms in schizophrenia.
abstract: SNAP-25 and syntaxin are presynaptic terminal SNARE proteins altered in amount and function in schizophrenia. In the ventral caudate, we observed 32% lower SNAP-25 and 26% lower syntaxin, but greater interaction between the two proteins using an in vitro assay. SNAP-25 has two isoforms, SNAP-25A and B, differing by only 9 amino acids, but with different effects on neurotransmission. A quantitative mass spectrometry assay was developed to measure total SNAP-25, and proportions of SNAP-25A and B. The assay had a good linear range (50- to 150-fold) and coefficient of variation (4.5%). We studied ventral caudate samples from patients with schizophrenia (n=15) previously reported to have lower total SNAP-25 than controls (n=13). We confirmed 27% lower total SNAP-25 in schizophrenia, and observed 31% lower SNAP-25A (P=0.002) with 20% lower SNAP-25B amounts (P=0.10). Lower SNAP-25A amount correlated with greater SNAP-25-syntaxin protein-protein interactions (r=-0.41, P=0.03); the level of SNAP-25B did not. Administration of haloperidol or clozapine to rats did not mimic the changes found in schizophrenia. The findings suggest that lower levels of SNAP-25 in schizophrenia may represent a greater effect of the illness on the SNAP-25A isoform. This in turn could contribute to the greater interaction between SNAP25 and syntaxin, and possibly disturb neurotransmission in the illness.
authors.affiliation: BC Mental Health and Addictions Research Institute, Vancouver, BC, Canada; Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Vilte E
authors.initials: VE
authors.lastname: Barakauskas
authors.affiliation: Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada.
authors.forename: Annie
authors.initials: A
authors.lastname: Moradian
authors.affiliation: BC Mental Health and Addictions Research Institute, Vancouver, BC, Canada; Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Alasdair M
authors.initials: AM
authors.lastname: Barr
authors.affiliation: BC Mental Health and Addictions Research Institute, Vancouver, BC, Canada; Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Beasley
authors.affiliation: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, USA; Macedonian Academy of Sciences and Arts, University "SS. Cyril and Methodius", Skopje, Macedonia; Department of Psychiatry, Columbia University, New York, NY, USA.
authors.forename: Gorazd
authors.initials: G
authors.lastname: Rosoklija
authors.affiliation: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, USA; Department of Psychiatry, Columbia University, New York, NY, USA.
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.affiliation: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, USA; Institute for Pathology, University "SS. Cyril and Methodius", Skopje, Macedonia; Department of Psychiatry, Columbia University, New York, NY, USA.
authors.forename: Boro
authors.initials: B
authors.lastname: Ilievski
authors.affiliation: Institute of Forensic Medicine, Criminology and Medical Deontology, University "SS. Cyril and Methodius", Skopje, Macedonia.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Stankov
authors.affiliation: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY, USA; Department of Psychiatry, Columbia University, New York, NY, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dwork
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Falkai
authors.affiliation: Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada. Electronic address: gmorin@bcgsc.ca.
authors.forename: Gregg B
authors.initials: GB
authors.lastname: Morin
authors.affiliation: BC Mental Health and Addictions Research Institute, Vancouver, BC, Canada; Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada. Electronic address: william.honer@ubc.ca.
authors.forename: William G
authors.initials: WG
authors.lastname: Honer
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D020033:Protein Isoforms; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D020033:Protein Isoforms; C494208:SNAP25 protein, human; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D003024:Clozapine; D006220:Haloperidol
keywords: Neural plasticity; Neurotransmission; Postmortem; SNARE proteins; Synapse