Synaptic Proteins in the Postmortem Anterior Cingulate Cortex in Schizophrenia: Relationship to Treatment and Treatment Response
Synaptic Proteins in the Postmortem Anterior Cingulate Cortex in Schizophrenia: Relationship to Treatment and Treatment Response
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DOI：
10.1038/npp.2014.57
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发表时间：
2014-08-01
影响因子：
7.6
通讯作者：
Roberts, Rosalinda C.
中科院分区：
文献类型：
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作者：
Barksdale, K. A.;Lahti, A. C.;Roberts, Rosalinda C.
前扣带皮层 (ACC) 是精神分裂症 (SZ) 中异常的几个大脑区域之一。在这里，我们使用死后 ACC 的蛋白质印迹比较了突触和线粒体功能标记：1）正常对照（NC，n = 13）与 SZ 受试者（n = 25）； NC、治疗抵抗性 SZ 和治疗反应性 SZ； 3) NC 和 SZ 使用典型或非典型抗精神病药物 (APD) 治疗。突触素、线粒体融合蛋白-2、vGLUT1 和钙调磷酸酶的蛋白质水平在 NC 组和 SZ 组之间没有差异，或者按治疗反应或 APD 类型划分的 NC 组与 SZ 组之间没有差异。在一些情况下，vGLUT1 的水平极低或不存在。缺乏vGLUT1的NC组比例显着低于SZ组。所有受试者之间存在几个正相关关系：1) 突触素和 vGLUT1； 2) 突触素和钙调神经磷酸酶； 3) 突触素和线粒体融合蛋白； 4)钙调神经磷酸酶和丝裂融合蛋白。突触素和钙调神经磷酸酶在应答者中呈正相关，并且这种相关性明显强于治疗抵抗性 SZ 受试者或 NC 受试者。突触素和钙调神经磷酸酶在非典型 APD 的 SZ 患者中呈正相关；这种相关性明显强于接受典型 APD 或 NC 治疗的 SZ 患者。 Mitofusin-2 和钙调磷酸酶在非典型 APD 和 NC 中的 SZ 患者中呈正相关；这种相关性在非典型 APD 患者中比典型 APD 患者或 NC 患者中更强。这些蛋白质在突触小泡循环、谷氨酸传输、线粒体融合和钙缓冲中发挥作用，它们之间的相关性很复杂，并且在各组之间受到不同的调节。
The anterior cingulate cortex (ACC) is one of several brain regions that are abnormal in schizophrenia (SZ). Here we compared markers of synapse and mitochondrial function using western blots of postmortem ACC in: 1) normal controls (NCs, n = 13) vs subjects with SZ (n = 25); NC, treatment-resistant SZ, and treatment-responsive SZ; and 3) NC and SZ treated with typical or atypical antipsychotic drugs (APDs). Protein levels of synaptophysin, mitofusin-2, vGLUT1, and calcineurin did not differ between the NC and SZ group as a whole, or the NCs vs the SZ group divided by treatment response or type of APDs. In several cases, the levels of vGLUT1 were minuscule or absent. The proportion of NCs lacking vGLUT1 was significantly less than that of the SZ groups. There were several positive correlations across all subjects between: 1) synaptophysin and vGLUT1; 2) synaptophysin and calcineurin; 3) synaptophysin and mitofusin; and 4) calcineurin and mitofusin. Synaptophysin and calcineurin were positively correlated in responders, and this correlation was significantly stronger than that in treatment-resistant SZ subjects or in NCs. Synaptophysin and calcineurin were positively correlated in SZ patients on atypical APDs; this correlation was significantly stronger than that in SZ patients on typical APDs or in NCs. Mitofusin-2 and calcineurin were positively correlated in SZ patients on atypical APDs and in NCs; this correlation was stronger in SZ patients on atypical rather than typical APDs or in NCs. The correlation between these proteins, which have roles in synaptic vesicle cycling, glutamate transmission, mitochondrial fusion, and calcium buffering, is complex and was differentially regulated among the groups.