Nowakowski Clara, Kaufmann Walter A, Adlassnig Christine, Maier Hans, Salimi Kayvon, Jellinger Kurt A, Marksteiner Josef
Department of Psychiatry, University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
Schizophr Res. 2002 Nov 1;58(1):43-53. doi: 10.1016/s0920-9964(01)00389-9.
Synaptic disturbances may play a key role in the pathophysiology of schizophrenia. This study was designed to further investigate possible synaptic alterations in the brains of chronic schizophrenic patients. Chromogranin B was applied as a marker for large dense core vesicles and synapsin I as a protein associated with the synaptic vesicle membrane. The distribution and density of chromogranin B-and synapsin I-like immunoreactivity in subregions of the hippocampus was compared between controls (n = 16) and patients with schizophrenia (n = 17). The overall distribution of hippocampal chromogranin B- and synapsin I-like immunoreactivity was similar in controls and in schizophrenic patients with the highest densities in the terminal field of mossy fibers and in the inner molecular layer of the dentate gyrus. In schizophrenic hippocampi, a significant reduction in the density of chromogranin B-like immunoreactivity was found in the CA4 and CA3 but not in the CA1 area of the dentate gyrus based on computerized image analysis. The loss of immunoreactivity was localized to mossy fibers and terminals surrounding hilar interneurons. Double-labelling immunohistochemistry revealed that synapsin I was co-expressed with chromogranin B in these neuronal structures and was also significantly reduced in schizophrenic hippocampi. The present study demonstrates an area-specific reduction of chromogranin B which is paralleled by a decrease of synapsin I. The loss of presynaptic proteins involved in distinct steps of exocytosis may cause complex synaptic disturbances in specific hippocampal subregions resulting in an imbalanced neurotransmitter availability in schizophrenic patients.
突触功能紊乱可能在精神分裂症的病理生理学中起关键作用。本研究旨在进一步探究慢性精神分裂症患者大脑中可能存在的突触改变。嗜铬粒蛋白B被用作大致密核心囊泡的标志物，而突触素I作为一种与突触囊泡膜相关的蛋白质。比较了对照组（n = 16）和精神分裂症患者组（n = 17）海马亚区中嗜铬粒蛋白B样和突触素I样免疫反应性的分布及密度。对照组和精神分裂症患者海马中嗜铬粒蛋白B样和突触素I样免疫反应性的总体分布相似，在苔藓纤维终末区和齿状回内分子层密度最高。在精神分裂症患者的海马中，基于计算机图像分析发现，齿状回的CA4和CA3区嗜铬粒蛋白B样免疫反应性密度显著降低，但CA1区未降低。免疫反应性缺失定位于苔藓纤维以及围绕海马门中间神经元的终末。双重标记免疫组化显示，突触素I在这些神经元结构中与嗜铬粒蛋白B共表达，在精神分裂症患者的海马中也显著减少。本研究表明嗜铬粒蛋白B存在区域特异性减少，同时伴有突触素I的减少。参与胞吐作用不同步骤的突触前蛋白缺失可能导致特定海马亚区出现复杂的突触功能紊乱，从而使精神分裂症患者神经递质可用性失衡。
