小柯机器人

英国伦敦大学学院Soyon Hong研究组发现，在阿尔茨海默病（AD）小鼠模型中，血管周围细胞通过SPP1诱导小胶质吞噬状态和突触吞噬。这一研究成果于2023年2月6日在线发表在国际学术期刊《自然—神经科学》上。

研究人员报道了分泌磷酸化蛋白1（SPP1/骨桥蛋白）主要由血管周围巨噬细胞上调，在较小程度上由血管周围成纤维细胞上调。血管周SPP1是小胶质细胞吞噬突触和上调吞噬标记物（包括C1qa、Grn和Ctsb）所需的，并以淀粉样蛋白β寡聚物存在。Spp1在阿尔茨海默病（AD）小鼠模型中表达缺失可防止突触丢失。此外，单细胞RNA测序和假定的细胞-细胞相互作用分析表明，血管周围SPP1诱导AD小鼠模型海马的小胶质细胞吞噬状态。总之，研究人员认为SPP1在血管周围细胞与小胶质细胞的相互作用中发挥了功能作用，从而在AD小鼠模型中调节小胶质细胞介导的突触吞噬。

据了解，AD的特征是突触丢失，这可能是由功能失调的小胶质细胞吞噬和补体激活引起的。然而，在AD中是什么信号驱动异常小胶质细胞介导的突触吞噬尚不清楚。

附：英文原文

Title: Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer’s disease

Author: De Schepper, Sebastiaan, Ge, Judy Z., Crowley, Gerard, Ferreira, Las S. S., Garceau, Dylan, Toomey, Christina E., Sokolova, Dimitra, Rueda-Carrasco, Javier, Shin, Sun-Hye, Kim, Jung-Seok, Childs, Thomas, Lashley, Tammaryn, Burden, Jemima J., Sasner, Michael, Sala Frigerio, Carlo, Jung, Steffen, Hong, Soyon

Issue&Volume: 2023-02-06

Abstract: Alzheimer’s disease (AD) is characterized by synaptic loss, which can result from dysfunctional microglial phagocytosis and complement activation. However, what signals drive aberrant microglia-mediated engulfment of synapses in AD is unclear. Here we report that secreted phosphoprotein 1 (SPP1/osteopontin) is upregulated predominantly by perivascular macrophages and, to a lesser extent, by perivascular fibroblasts. Perivascular SPP1 is required for microglia to engulf synapses and upregulate phagocytic markers including C1qa, Grn and Ctsb in presence of amyloid-β oligomers. Absence of Spp1 expression in AD mouse models results in prevention of synaptic loss. Furthermore, single-cell RNA sequencing and putative cell–cell interaction analyses reveal that perivascular SPP1 induces microglial phagocytic states in the hippocampus of a mouse model of AD. Altogether, we suggest a functional role for SPP1 in perivascular cells-to-microglia crosstalk, whereby SPP1 modulates microglia-mediated synaptic engulfment in mouse models of AD.

DOI: 10.1038/s41593-023-01257-z

Source: https://www.nature.com/articles/s41593-023-01257-z

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