弓形虫感染引起小胶质细胞与神经元的接触以及细胞体周边抑制性突触丧失  

Toxoplasma infection induces microglia-neuron contact and the loss of perisomatic inhibitory synapses

作　　者：Carrillo GL Ballard VA Glausen T Boone Z Teamer J Hinkson CL Wohlfert EA Blader IJ Fox MA 杜一星(编译) 

机构地区：[1]Center for Neurobiology Research,Fralin Biomedical Research Institute at Virginia Tech Carilion,Roanoke,Virginia,USA [2]Graduate Program in Translational Biology,Medicine,and Health,Virginia Tech,Blacksburg,Virginia,USA [3]Roanoke Valley Governor's School,Roanoke,Virginia,USA [4]Department of Microbiology and Immunology,University at Buffalo,Buffalo,New York,USA [5]School of Neuroscience,Virginia Tech,Blacksburg,Virginia,USA [6]FBRI neuroSURF Program,Roanoke,Virginia,USA [7]Virginia Tech Carilion School of Medicine,Roanoke,Virginia,USA [8]Department of Biological Sciences,Virginia Tech,Blacksburg,Virginia,USA [9]Department of Pediatrics,Virginia Tech Carilion School of Medicine,Roanoke,Virginia,USA [10]不详

出　　处：《神经损伤与功能重建》2020年第3期F0004-F0004,共1页Neural Injury and Functional Reconstruction

摘　　要：大脑内的感染和炎症会引起神经元连通性和功能的改变。细胞内的原生动物寄生虫,弓形虫,是一种感染脑部的病原体,可引起脑炎和癫痫发作。这种寄生虫的持续感染还与行为改变和发生精神疾病(包括精神分裂症)的风险增加有关。目前来自人类和小鼠模型的研究证据表明,癫痫发作和精神分裂症均由抑制性突触的丧失或功能障碍引起。与此相符,我们最近报道了持续性弓形虫感染改变谷氨酸脱羧酶67(GAD67)的分布,该酶在抑制性突触中催化GABA的合成。这些变化可能反映突触前装置在抑制性神经元中的重新分布或抑制性神经末梢的丧失。为了直接评估后者的可能性,我们采用序列块面扫描电子显微镜(SBFSEM)并量化寄生虫感染后新皮质和海马中的细胞体周边抑制性突触。持续感染不仅导致明显的细胞体周边突触丧失,而且还诱导髓样来源的细胞对神经元细胞体的包封。免疫组织化学、遗传和超微结构分析显示,这些髓样来源的细胞包括活化的小胶质细胞。最后,超微结构分析确定了包膜于细胞体周围神经末梢的髓样来源的细胞,提示它们可能会主动置换或吞噬突触元件。因此,这些结果表明,活化的小胶质细胞有助于寄生虫感染后细胞体周围抑制突触损失,并对于弓形虫的持续感染可能如何导致癫痫发作和精神疾病提供了一种新的机制。Infection and inflammation within the brain induces changes in neuronal connectivity and function. The intracellular protozoan parasite, Toxoplasma gondii, is one pathogen that infects the brain and can cause encephalitis and seizures. Persistent infection by this parasite is also associated with behavioral alterations and an increased risk for developing psychiatric illness, including schizophrenia. Current evidence from studies in humans and mouse models suggest that both seizures and schizophrenia result from a loss or dysfunction of inhibitory synapses. In line with this, we recently reported that persistent T.gondii infection alters the distribution of glutamic acid decarboxylase 67(GAD67), an enzyme that catalyzes GABA synthesis in inhibitory synapses. These changes could reflect a redistribution of presynaptic machinery in inhibitory neurons or a loss of inhibitory nerve terminals. To directly assess the latter possibility, we employed serial block face scanning electron microscopy(SBFSEM) and quantified inhibitory perisomatic synapses in neocortex and hippocampus following parasitic infection. Not only did persistent infection lead to a significant loss of perisomatic synapses, it induced the ensheathment of neuronal somata by myeloid-derived cells. Immunohistochemical, genetic, and ultrastructural analyses revealed that these myeloid-derived cells included activated microglia. Finally, ultrastructural analysis identified myeloid-derived cells enveloping perisomatic nerve terminals, suggesting they may actively displace or phagocytose synaptic elements. Thus, these results suggest that activated microglia contribute to perisomatic inhibitory synapse loss following parasitic infection and offer a novel mechanism as to how persistent T. gondii infection may contribute to both seizures and psychiatric illness.

关 键 词：弓形虫 海马 抑制性突触 小胶质细胞 新皮质 细胞体周边突触 

分 类 号：R741[医药卫生—神经病学与精神病学] R741.02[医药卫生—临床医学]