Distribution of HLA-DR-positive microglia in schizophrenia reflects impaired cerebral lateralization
Distribution of HLA-DR-positive microglia in schizophrenia reflects impaired cerebral lateralization
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DOI：
10.1007/s00401-006-0090-8
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发表时间：
2006-09-01
影响因子：
12.7
通讯作者：
Bogerts, Bernhard
中科院分区：
文献类型：
--
作者：
Steiner, Johann;Mawrin, Christian;Bogerts, Bernhard
免疫学改变已被证明在精神分裂症患者的外周血和脑脊液中，而以前的尸检研究提供了一个不一致的图片，小胶质细胞在精神分裂症的背景下的作用。小胶质细胞活化是CNS微环境变化的敏感指标，如炎症和神经退行性过程。本尸检研究的目的是检查HLA II类（HLA-DR）表达的小胶质细胞在大脑区域，特别是相关的精神分裂症，关于半球偏侧化。对16例精神分裂症患者和16例正常对照者的背外侧前额叶皮层（DLPFC）、前扣带回皮层（ACC）、海马和内侧背丘脑（MD）进行了研究。免疫染色发现在所有的大脑区域，并不限于巨噬细胞样阿米巴样细胞，但也出现在分支细胞。区域特异性HLA-DR阳性细胞密度在精神分裂症患者和对照组之间无显著差异。然而，阿米巴样小胶质细胞偏向右半球的健康受试者，但不是在精神分裂症组（P=0.01）。死亡时间与ACC/DLPFC分支细胞数（P=0.01/0.04）和海马变形样细胞密度（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。单个病例分析显示，两名在急性精神病期间自杀的精神分裂症患者的ACC和MD中的小胶质细胞数量高度升高。总之，目前的数据表明，小胶质细胞增生的情况下，但减少大脑偏侧的阿米巴样小胶质细胞在精神分裂症。
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.