使用体内化学遗传学，课题组研究人员证明了神经元过度活跃诱导区域特异性，C1q依赖性突触丧失在成人海马。在阿尔茨海默病小鼠模型中，抑制穿孔通路过度活跃可减少局部淀粉样蛋白-β量和C1q沉积，并部分挽救突触损失。结合空间转录组学、活细胞跟踪和超分辨率显微镜，该课题组研究人员发现了成人海马中分泌抗体的b系细胞与生理条件下C1q介导的活性依赖性突触损失的关联。总之，这些发现将神经元过度活跃与成人大脑中C1q介导的突触丢失联系起来，并暗示免疫球蛋白在这一过程中起着重要作用。
研究人员表示，补体成分1q （C1q）是经典补体级联的启动物，在发育和疾病中介导突触消除，但其在突触上沉积的触发因素尚不清楚。
附：英文原文
Title: C1q and immunoglobulins mediate activity-dependent synapse loss in the adult brain
Author: Gerard Crowley, Minjung Kim, Nathanael O’Neill, Emir Turkes, Fateme Ghasemi, Luca Giudice, Sebastiaan De Schepper, Benjy J. Y. Tan, Benito Maffei, Laís S. S. Ferreira, Julie Rebejac, Javier Rueda-Carrasco, Margarita Toneva, John Christian Fajardo, Judy Z. Ge, Zhengyue Grace Yang, Paula Korhonen, Phillip Muckett, Damaris Bennett, Camille Paoletti, Tammie T. M. Sow, David A. Posner, Annerieke Sierksma, Dimitra Sokolova, Viktoras Konstantellos, Leen Ali, Kiavash Movahedi, Andrew F. MacAskill, Victor L. J. Tybulewicz, Tarja Malm, Gabriele Lignani, Menna R. Clatworthy, Soyon Hong
Issue&Volume: 2026-07-09
Abstract: Complement component 1q (C1q), the initiator of the classical complement cascade, mediates synaptic elimination in development and disease, yet the triggers for its deposition on synapses remain unclear. Using in vivo chemogenetics, we demonstrate that neuronal hyperactivity induces region-specific, C1q-dependent synapse loss in the adult hippocampus. Suppressing perforant pathway hyperactivity in a mouse model of Alzheimer’s disease reduced local amyloid-β amounts and C1q deposition and partially rescued synapse loss. Combining spatial transcriptomics, live cell tracking, and super-resolution microscopy, we identified association of antibody-secreting B-lineage cells in the adult hippocampus with activity-dependent, C1q-mediated synapse loss under physiological conditions. Together, these findings link neuronal hyperactivity to C1q-mediated synapse loss in the adult brain and implicate immunoglobulins as players in this process.
DOI: adv1219
Source: https://www.science.org/doi/10.1126/science.adv1219