麻省大学陈医学院Dorothy P. Schafer研究团队取得一项新突破。他们揭示了小胶质细胞-星形胶质细胞串扰通过Wnt信号调节突触重塑。该研究于2025年9月10日发表于国际一流学术期刊《细胞》杂志上。
研究小组在出生后小鼠中进行须去除，以诱导桶状皮质中活动依赖性突触的去除。该课题组人员发现星形胶质细胞在这种情况下不会吞噬突触。相反，星形胶质细胞在小胶质细胞介导的突触吞噬之前减少了与突触的接触。该研究团队进一步表明，星形胶质细胞-突触接触的减少依赖于神经元到小胶质细胞fractalkine配体受体（CX3CL1-CX3CR1）信号传导下游小胶质细胞释放的wnt。这些结果证明了一种活动依赖机制，通过这种机制，小胶质细胞指导星形胶质细胞与突触的相互作用，为小胶质细胞移除突触提供了一个允许的环境。课题组进一步表明，这种机制对于在不断变化的感觉环境中重塑突触至关重要，并且这种信号在几种疾病背景下上调。
据了解，星形胶质细胞和小胶质细胞是活动依赖性突触重塑的关键调节因子，在神经活动变化的反应中吞噬和移除突触。然而，这些细胞沟通协调这一过程的程度仍然是一个悬而未决的问题。
附：英文原文
Title: Microglia-astrocyte crosstalk regulates synapse remodeling via Wnt signaling
Author: Travis E. Faust, Yi-Han Lee, Ciara D. O’Connor, Margaret A. Boyle, Georgia Gunner, Violeta Durán-Laforet, Loris L. Ferrari, Robert E. Murphy, Ana Badimon, Kristina Sakers, Cagla Eroglu, Pinar Ayata, Anne Schaefer, Dorothy P. Schafer
Issue&Volume: 2025-09-10
Abstract: Astrocytes and microglia are emerging key regulators of activity-dependent synapse remodeling that engulf and remove synapses in response to changes in neural activity. Yet, the degree to which these cells communicate to coordinate this process remains an open question. Here, we use whisker removal in postnatal mice to induce activity-dependent synapse removal in the barrel cortex. We show that astrocytes do not engulf synapses in this paradigm. Instead, astrocytes reduce contact with synapses prior to microglia-mediated synapse engulfment. We further show that the reduced astrocyte-synapse contact is dependent on the release of Wnts from microglia downstream of neuron-to-microglia fractalkine ligand-receptor (CX3CL1-CX3CR1) signaling. These results demonstrate an activity-dependent mechanism by which microglia instruct astrocyte-synapse interactions, providing a permissive environment for microglia to remove synapses. We further show that this mechanism is critical to remodel synapses in a changing sensory environment and that this signaling is upregulated in several disease contexts.
DOI: 10.1016/j.cell.2025.08.023
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00978-X