Steiner Johann, Mawrin Christian, Ziegeler Anke, Bielau Hendrik, Ullrich Oliver, Bernstein Hans-Gert, Bogerts Bernhard
Department of Psychiatry, University of Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany.
Acta Neuropathol. 2006 Sep;112(3):305-16. doi: 10.1007/s00401-006-0090-8. Epub 2006 Jun 17.
Immunological alterations have been demonstrated in peripheral blood and cerebrospinal fluid of patients with schizophrenia, while previous postmortem studies have provided an inconsistent picture as to the role of microglia in the context of schizophrenia. Microglial activation is a sensitive indicator of changes in the CNS microenvironment, such as inflammatory and neurodegenerative processes. The aim of the present postmortem study was to examine HLA class II (HLA-DR) expression on microglia in brain regions which are particularly relevant for schizophrenia, with regard to hemispheric lateralization. Dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), hippocampus and mediodorsal thalamus (MD) were studied in 16 cases with schizophrenia and 16 control subjects. Immunostaining was found in all brain regions and was not restricted to macrophage-like ameboid cells, but also appeared in ramified cells. Region-specific HLA-DR-positive cell density was not significantly different between cases with schizophrenia and controls. However, ameboid microglial cells were lateralized towards the right hemisphere in healthy subjects but not in the schizophrenia group (P=0.01). Postmortem interval correlated with ramified cell numbers in ACC/DLPFC (P=0.01/0.04) and ameboid cell density in hippocampus (P=0.03). Age, gender, duration of disease, medication dosage, storage delay and whole brain volume had no effect. Single case analysis revealed highly elevated microglial cell numbers in ACC and MD of two schizophrenic patients who had committed suicide during acute psychosis. In conclusion, the present data suggest the absence of microgliosis but decreased cerebral lateralization of ameboid microglia in schizophrenia.
精神分裂症患者的外周血和脑脊液中已证实存在免疫改变，而先前的尸检研究对于小胶质细胞在精神分裂症中的作用呈现出不一致的情况。小胶质细胞活化是中枢神经系统微环境变化（如炎症和神经退行性过程）的敏感指标。本尸检研究的目的是研究与精神分裂症特别相关的脑区中小胶质细胞上的人类白细胞抗原II类（HLA - DR）表达，涉及半球侧化情况。对16例精神分裂症患者和16名对照受试者的背外侧前额叶皮质（DLPFC）、前扣带回皮质（ACC）、海马体和背内侧丘脑（MD）进行了研究。在所有脑区均发现免疫染色，且不仅限于巨噬细胞样阿米巴样细胞，也出现在分支状细胞中。精神分裂症患者与对照组之间区域特异性HLA - DR阳性细胞密度无显著差异。然而，在健康受试者中，阿米巴样小胶质细胞偏向右侧半球，而在精神分裂症组中则不然（P = 0.01）。尸检间隔与ACC/DLPFC中的分支状细胞数量（P = 0.01/0.04）以及海马体中的阿米巴样细胞密度（P = 0.03）相关。年龄、性别、病程、药物剂量、储存延迟和全脑体积均无影响。单病例分析显示，两名在急性精神病期间自杀的精神分裂症患者的ACC和MD中小胶质细胞数量高度升高。总之，目前的数据表明精神分裂症中不存在小胶质细胞增生，但阿米巴样小胶质细胞的脑侧化减少。
