研究人员在皮质多发性硬化症（MS）小鼠模型中使用功能性和结构体内成像来证明皮质炎症发作破坏了皮质回路活动，并与广泛但短暂的树突棘丧失相吻合。实验结果显示出局部钙积累，随后通过侵袭巨噬细胞或活化的小胶质细胞而去除。集落刺激因子1受体的新拮抗剂靶向吞噬细胞的激活可防止皮质突触丢失。
总的来说，这项研究将突触丧失确定为炎症性灰质病变的关键病理特征，可通过免疫调节来治疗。
据介绍，皮质病理在神经炎性疾病MS患者中导致慢性认知障碍。这种灰质发炎如何影响神经元的结构和功能尚不清楚。
附：英文原文
Title: Phagocyte-mediated synapse removal in cortical neuroinflammation is promoted by local calcium accumulation
Author: Mehrnoosh Jafari, Adrian-Minh Schumacher, Nicolas Snaidero, Emily M. Ullrich Gavilanes, Tradite Neziraj, Virg Kocsis-Jutka, Daniel Engels, Tanja Jrgens, Ingrid Wagner, Juan Daniel Flrez Weidinger, Stephanie S. Schmidt, Eduardo Beltrn, Nellwyn Hagan, Lisa Woodworth, Dimitry Ofengeim, Joseph Gans, Fred Wolf, Mario Kreutzfeldt, Ruben Portugues, Doron Merkler, Thomas Misgeld, Martin Kerschensteiner
Issue&Volume: 2021-01-25
Abstract: Cortical pathology contributes to chronic cognitive impairment of patients suffering from the neuroinflammatory disease multiple sclerosis (MS). How such gray matter inflammation affects neuronal structure and function is not well understood. In the present study, we use functional and structural in vivo imaging in a mouse model of cortical MS to demonstrate that bouts of cortical inflammation disrupt cortical circuit activity coincident with a widespread, but transient, loss of dendritic spines. Spines destined for removal show local calcium accumulations and are subsequently removed by invading macrophages or activated microglia. Targeting phagocyte activation with a new antagonist of the colony-stimulating factor 1 receptor prevents cortical synapse loss. Overall, our study identifies synapse loss as a key pathological feature of inflammatory gray matter lesions that is amenable to immunomodulatory therapy. Synapse loss is prominent in the cortex in multiple sclerosis (MS). In a cortical MS model, Jafari et al. show that phagocytes remove synapses by engulfment, which is triggered by local calcium accumulations and prevented by blocking colony-stimulating factor 1 signaling.
DOI: 10.1038/s41593-020-00780-7
Source: https://www.nature.com/articles/s41593-020-00780-7
Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex
本期文章：《自然—神经科学》：Online/在线发表
