Abnormalities of SNARE mechanism proteins in anterior frontal cortex in severe mental illness
Abnormalities of SNARE mechanism proteins in anterior frontal cortex in severe mental illness
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DOI：
10.1093/cercor/12.4.349
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发表时间：
2002-04-01
期刊：
影响因子：
3.7
通讯作者：
Trimble, WS
中科院分区：
文献类型：
--
作者：
Honer, WG;Falkai, P;Trimble, WS
神经连接的基本分子组成是SNARE（SNAP受体）蛋白复合物，其由三种蛋白质，syntaxin，SNAP-25和VAMP组成。在适当的条件下，SNARE复合物可以在体外形成。为了研究SNARE蛋白或其相互作用的失调在严重精神障碍中可能异常的假设，在死后的前额叶皮质匀浆中研究了三种SNARE蛋白和复合物。ELISA被用来量化SNARE蛋白免疫反应的皮质匀浆从四组：精神分裂症患者谁死于自杀以外的原因（n = 6），精神分裂症患者和自杀（n = 7），抑郁症患者和自杀（n = 11），和对照组（n = 11）。证实了组间SNARE蛋白免疫反应性模式的差异[Wilks' Lambda F（9，68）= 3.57，P = 0.001]。逐个蛋白质分析表明，在精神分裂症非自杀组中SNAP-25免疫反应性显著降低[相对于对照降低28%，F（3，31）= 6，45，P = 0.002，Student-Newman-Keuls检验，P < 0.01]。SNARE蛋白和突触素免疫反应性之间的相互关系在对照组中较高，但在其他组中较低，进一步表明这些蛋白质之间的关系紊乱。使用免疫印迹法研究SNARE复合物在体外形成的程度。对于SNAP-25 [Wilks' Lambda F（3，31）= 4.76，P = 0.008]和突触融合蛋白免疫染色[Wilks' Lambda F（3，31）= 9.16，P = 0.0002]鉴定的SNARE复合物，观察到与组成员关系相关的显著差异。在以自杀为死因的两组中，异源三聚体SNARE复合物中存在的SNAP-25和突触融合蛋白比其他分子形式相对更多，SNARE复合物中的这些异常可能代表严重精神障碍中神经连接异常的分子底物。
A fundamental molecular component of neural connectivity is the SNARE (SNAP receptor) protein complex, which consists of three proteins, syntaxin, SNAP-25 and VAMP. Under appropriate conditions, the SNARE complex can be formed in vitro. To investigate the hypothesis that dysregulation of SNARE proteins or their interactions could be abnormal in severe mental disorders, the three SNARE proteins and the complex were studied in post-mortem anterior frontal cortex homogenates. An ELISA was used to quantify SNARE protein immunoreactivities in cortical homogenates from four groups: patients with schizophrenia who died of causes other than suicide (n = 6), patients with schizophrenia and suicide (n = 7), patients with depression and suicide (n = 11), and controls (n = 11). Differences between groups in patterns of SNARE protein immunoreactivities were demonstrated [Wilks' Lambda F(9,68) = 3.57, P = 0.001]. Protein-by-protein analyses indicated a significant reduction in SNAP-25 immuno reactivity in the schizophrenia non-suicide group [28% decrease relative to controls, F(3,31) = 6,45, P = 0.002, Student-Newman-Keuls test, P < 0.01]. The intercorrelations between SNARE protein and synaptophysin immunoreactivities were high in controls, but lower in the other groups, further indicating disturbances in relationships between these proteins. The extent of SNARE complex formation in vitro was studied using immunoblotting. Significant differences related to group membership were observed for the SNARE complexes identified by SNAP-25 [Wilks' Lambda F(3,31) = 4.76, P = 0.008] and by syntaxin immunostaining [Wilks' Lambda F(3,31) = 9.16, P = 0.0002]. In both groups with suicide as a cause of death, relatively more SNAP-25 and syntaxin was present in the heterotrimeric SNARE complex than in other molecular forms, These abnormalities in the SNARE complex could represent a molecular substrate for abnormalities of neural connectivity in severe mental disorders.