Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.
Biomedical Center, Faculty of Medicine, Ludwig-Maximilians University Munich, Munich, Germany.
Nat Neurosci. 2021 Mar;24(3):355-367. doi: 10.1038/s41593-020-00780-7. Epub 2021 Jan 25.
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.
皮质病理学导致患有神经炎症性疾病多发性硬化症 (MS) 的患者出现慢性认知障碍。皮质炎症如何影响神经元的结构和功能还不是很清楚。在本研究中，我们使用皮质 MS 小鼠模型中的功能和结构体内成像来证明皮质炎症的发作会干扰皮质回路活动，同时导致广泛但短暂的树突棘丢失。注定要被去除的树突棘会出现局部钙积累，随后被入侵的巨噬细胞或活化的小胶质细胞去除。用集落刺激因子 1 受体的新型拮抗剂靶向吞噬细胞激活可防止皮质突触丢失。总的来说，我们的研究确定了突触丢失是炎症性灰质病变的一个关键病理特征，可通过免疫调节治疗来改善。
