Eastwood S L, Harrison P J
University Department of Psychiatry, Warneford Hospital, Radcliffe Infirmary, Oxford, U.K.
Neuroscience. 1995 Nov;69(2):339-43. doi: 10.1016/0306-4522(95)00324-c.
Synaptic alterations have been suggested, largely on theoretical grounds, to occur in the brain in schizophrenia. The messenger RNA encoding synaptophysin, a presynaptic terminal protein, is reduced in the medial temporal lobe in the disease, but immunocytochemical and immunoblotting data have not produced clear evidence for a loss of the encoded protein. Here we have used immunoautoradiography with an antisynaptophysin monoclonal antibody and a 35S-labelled secondary antibody in medial temporal lobe sections from 11 schizophrenics and 14 matched controls. In the schizophrenic cases there was an overall loss of synaptophysin (P < 0.02). Analysis by subfield showed significant reductions in the right dentate gyrus molecular layer, subiculum and parahippocampal gyrus, with similar trends in most other subfields. These data confirm that synaptophysin expression is decreased within the medial temporal lobe in schizophrenia. In the respect that synaptophysin is a marker of synaptic density, our findings suggest that reduced synaptic density may be a feature of the molecular neuropathology of the disease.
基于理论依据，人们认为精神分裂症患者大脑中会出现突触改变。编码突触素（一种突触前终末蛋白）的信使核糖核酸在该疾病的内侧颞叶中减少，但免疫细胞化学和免疫印迹数据并未提供明确证据证明编码蛋白的缺失。在此，我们使用抗突触素单克隆抗体和35S标记的二抗对11例精神分裂症患者和14例匹配对照的内侧颞叶切片进行免疫放射自显影。在精神分裂症病例中，突触素总体上有所减少（P < 0.02）。按亚区域分析显示，右侧齿状回分子层、海马下托和海马旁回有显著减少，大多数其他亚区域也有类似趋势。这些数据证实精神分裂症患者内侧颞叶内突触素表达降低。鉴于突触素是突触密度的标志物，我们的研究结果表明突触密度降低可能是该疾病分子神经病理学的一个特征。
