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Barakauskas, Vilte E.; Moradian, Annie; Barr, Alasdair M.; Beasley, Clare L.; Rosoklija, Gorazd; Mann, J. John; Ilievski, Boro; Stankov, Aleksandar; Dwork, Andrew J.; Falkai, Peter ORCID: 0000-0003-2873-8667; Morin, Gregg B.; Honer, William G. (2016): Quantitative mass spectrometry reveals changes in SNAP-25 isoforms in schizophrenia. In: Schizophrenia Research, Vol. 177, No. 1-3: pp. 44-51
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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. (C) 2016 Elsevier B.V. All rights reserved.