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未分化型与偏执型精神分裂症患者纹状体中突触变化的差异

Differential synaptic changes in the striatum of subjects with undifferentiated versus paranoid schizophrenia.

作者信息

Roberts Rosalinda C, Roche Joy K, Conley Robert R

机构信息

Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

出版信息

Synapse. 2008 Aug;62(8):616-27. doi: 10.1002/syn.20534.

DOI:10.1002/syn.20534
PMID:18509852
Abstract

Subjects with schizophrenia (SZ) have an increased density of synapses characteristic of corticostriatal or thalamostriatal glutamatergic inputs in the caudate matrix and putamen patches. SZ is a heterogeneous disease in many aspects including symptoms. The purpose of the present study was to determine if the synaptic organization in two different DSM-i.v. subgroups of SZ was differentially affected. Postmortem striatal tissue was obtained from the Maryland Brain Collection from normal controls (NC), chronic paranoid SZs (SZP), and chronic undifferentiated SZs (SZU). Tissue was prepared for calbindin immunocytochemistry to identify patch matrix compartments, prepared for electron microscopy and analyzed using stereological methods. The synaptic density of asymmetric synapses, characteristic of glutamatergic inputs, was elevated equivalently in striatal patches in the SZP and SZU versus NC. The SZU also had an increased density of asymmetric synapses in the striatal matrix compared to NC. Moreover, symmetric axospinous synapses, characteristic of intrinsic inhibitory inputs and dopaminergic afferents, showed a dichotomy in synaptic density between the SZU and SZP in the striatal and caudate matrix. These data show discreet differences in synaptic organization between SZU and SZP and/or NCs. The results suggest that abnormal corticostriatal and/or corticothalamic inputs to striatal patches may be related to limbic dysfunction, which is perturbed in both subtypes of SZ. The selective increase in axospinous synapses in the matrix of the SZU subgroup compared to the SZP may be related to more severe cognitive problems in that subset of SZ compared to SZP.

摘要

精神分裂症(SZ)患者尾状核基质和壳核斑块中,具有皮质纹状体或丘脑纹状体谷氨酸能输入特征的突触密度增加。SZ在包括症状在内的许多方面都是一种异质性疾病。本研究的目的是确定SZ的两个不同DSM-Ⅳ亚组中的突触组织是否受到不同影响。从马里兰脑库获取正常对照(NC)、慢性偏执型SZ(SZP)和慢性未分化型SZ(SZU)的死后纹状体组织。将组织制备用于钙结合蛋白免疫细胞化学以识别斑块-基质区室,制备用于电子显微镜检查并使用体视学方法进行分析。与NC相比,SZP和SZU的纹状体斑块中,具有谷氨酸能输入特征的不对称突触的突触密度同等升高。与NC相比,SZU的纹状体基质中不对称突触的密度也增加。此外,具有内在抑制性输入和多巴胺能传入特征的对称轴棘突触,在纹状体和尾状核基质中,SZU和SZP的突触密度存在差异。这些数据显示了SZU与SZP和/或NC之间在突触组织上的细微差异。结果表明,纹状体斑块的异常皮质纹状体和/或皮质丘脑输入可能与边缘系统功能障碍有关,这在SZ的两种亚型中均受到干扰。与SZP相比,SZU亚组基质中轴棘突触的选择性增加可能与该亚型SZ中比SZP更严重的认知问题有关。

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