CTR1 and Dysbindin-1 in postmortem schizophrenia hippocampus

Several schizophrenia brain regions exhibit decreased dysbindin-1 including the hippocampus. We hypothesized that there would be less dysbindin-1 and CTR1 levels in the hippocampus in SZP and performed a quantitative immunohistochemical study on controls and SZP (n=10 per group). The hippocampus proper, dentate gyrus, entorhinal cortex, and subiculum were richly immunolabeled for CTR1 in both controls and SZP. Qualitatively, CTR1 immunolabeling was present in the same cell types in both groups. Only the optical density of CTR1 immunolabeling in the entorhinal cortex and dentate gyrus showed significant differences between groups. In the superficial area of the entorhinal cortex, both neuropil and cells showed lower optical density values in the SZP than in controls. The opposite pattern was observed in the molecular layer of the dentate gyrus, where SZP had significantly higher optical density values than did controls. The density and distribution of dysbindin-1 immunolabeling was similar between groups with no significant differences. These results suggest laminar specific alterations of copper transport within SZP that is not directly caused by decreased dysbindin-1. Therefore, dysbindin-1 may be sufficient but not necessary to induce abnormal copper transport in SZP.多种精神分裂症受累脑区的dysbindin-1（dysbindin-1）表达水平下调，其中包括海马体。本研究假设精神分裂症（SZP）患者海马体内的dysbindin-1与CTR1（铜转运蛋白1）水平均会降低，随后我们针对对照组与SZP患者组（每组n=10）开展了定量免疫组织化学研究。在对照组与SZP患者组中，海马固有区、齿状回、内嗅皮层以及下托均出现了较强的CTR1免疫标记信号。从定性层面来看，两组样本中CTR1免疫标记所靶向的细胞类型完全一致。仅在内嗅皮层与齿状回的CTR1免疫标记光密度上，两组间存在显著差异。在内嗅皮层的表层区域，SZP患者组的神经纤维网与神经元的光密度值均低于对照组。而在齿状回的分子层则观察到了相反的变化模式：SZP患者组的光密度值显著高于对照组。两组样本中dysbindin-1免疫标记的密度与分布均无显著差异。上述结果表明，SZP患者体内存在层状特异性的铜转运异常，且该异常并非由dysbindin-1水平下调直接引发。由此可见，dysbindin-1或可单独诱导SZP患者的铜转运异常，但并非该异常发生的必要条件。