Quantitative mass spectrometry reveals changes in SNAP-25 isoforms in schizophrenia

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• 作者：Vilte E. Barakauskas^a ; ^b ; Annie Moradian^c ; Alasdair M. Barr^a ; ^e ; Clare L. Beasley^a ; ^b ; Gorazd Rosoklija^f ; ^g ; ^l ; J. John Mann^f ; ^l ; Boro Ilievski^f ; ^h ; ^l ; Aleksandar Stankovⁱ ; Andrew J. Dwork^f ; ^j ; ^l ; Peter Falkai^k ; Gregg B. Morin^c ; ^d ; ^{gmorin@bcgsc.ca" class="auth_mail" title="E-mail the corresponding author} ; William G. Honer^a ; ^b ; ^{william.honer@ubc.ca" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Neural plasticity ; SNARE proteins ; Postmortem ; Neurotransmission ; Synapse
• 刊名：Schizophrenia Research
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：177
• 期：1-3
• 页码：44-51
• 全文大小：823 K

文摘

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.