Department of Psychiatry, Ruhr University Bochum, LWL University Hospital, Germany.
Schizophr Res. 2011 Sep;131(1-3):96-100. doi: 10.1016/j.schres.2011.06.018. Epub 2011 Jul 12.
Inflammatory and immunological processes interfering with brain development are discussed as one cause of schizophrenia. Various signs of overactivation of the immune system were often found in this disease. Based on post-mortem analysis showing an increased number of activated microglial cells in patients with schizophrenia, it can be hypothesized that these cells contribute to disease pathogenesis and may actively be involved in gray matter loss observed in such patients. In the present study, PolyI:C incubation of pregnant dams was used as animal model of schizophrenia, and the number and shape of microglia were assessed in the offspring in the early phase of this disease, using fluorescence immunostaining (Iba1). Descendants of mice exposed to PolyI:C at embryonic day 9 showed higher number of microglial cells in the hippocampus and striatum, but not in the frontal cortex at postnatal day 30, which is similarly to adolescence in man, as compared to those exposed to saline. Furthermore, offspring microglia from PolyI:C treated mothers were morphologically characterized by a reduced arborization indicative for a status of higher activation compared to the offspring microglia from vehicle treated mice. This study supports the hypothesis that maternal infection during embryogenesis contributes to microglial activation in the offspring, which may therefore represent a contributing factor to the pathogenesis of schizophrenia and underlines the need for new pharmacological treatment options in this regard.
炎症和免疫过程干扰大脑发育被认为是精神分裂症的一个原因。在这种疾病中，经常发现免疫系统过度激活的各种迹象。基于死后分析显示精神分裂症患者中激活的小胶质细胞数量增加，可以假设这些细胞有助于疾病的发病机制，并可能积极参与在这些患者中观察到的灰质损失。在本研究中，聚肌胞孵育怀孕的母鼠作为精神分裂症的动物模型，使用荧光免疫染色（Iba1）评估疾病早期后代中小胶质细胞的数量和形态。在出生后 30 天，与生理盐水暴露的后代相比，在胚胎第 9 天暴露于聚肌胞的小鼠的后代在海马体和纹状体中显示出更高数量的小胶质细胞，但在前额叶皮层中没有，这与人类青春期相似。此外，与来自载体处理小鼠的后代小胶质细胞相比，来自聚肌胞处理的母鼠的后代小胶质细胞的形态特征为分支减少，表明其处于更高的激活状态。这项研究支持了这样一种假设，即胚胎发育期间的母体感染导致后代中小胶质细胞的激活，因此可能是精神分裂症发病机制的一个促成因素，并强调了在这方面需要新的药物治疗选择。
