Microglia-astrocyte crosstalk regulates synapse remodeling via Wnt signaling.
Microglia-astrocyte crosstalk regulates synapse remodeling via Wnt signaling.
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小胶质细胞-星形胶质细胞串扰通过 Wnt 信号传导调节突触重塑。
DOI：
10.1101/2024.02.08.579178
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Schafer,DorothyP
中科院分区：
文献类型：
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作者：
Faust,TravisE;Lee,Yi-Han;O'Connor,CiaraD;Boyle,MargaretA;Gunner,Georgia;Badimon,Ana;Ayata,Pinar;Schaefer,Anne;Schafer,DorothyP
星形胶质细胞和小胶质细胞是活动依赖性突触重塑的新兴关键调节因子，它们响应于神经活动的变化而吞噬和移除突触。然而，这些细胞在多大程度上交流以协调这一过程仍然是一个悬而未决的问题。在这里，我们在出生后的小鼠中使用胡须去除来诱导桶皮质中的活动依赖性突触去除。我们发现，星形胶质细胞不吞噬突触在这种模式。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它们与突触的接触。我们进一步表明，减少星形胶质细胞与突触的接触是依赖于小胶质细胞CX 3CL 1-CX 3CR 1信号和Wnt从小胶质细胞的晶须去除后释放。这些结果表明，小胶质细胞指示星形胶质细胞-突触相互作用的活性依赖性机制，然后为小胶质细胞去除突触提供了一个允许的环境。我们进一步表明，这种机制是至关重要的重塑突触在不断变化的感觉环境，这种信号在几种疾病的情况下上调。
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 their contact with synapses prior to microglia-mediated synapse engulfment. We further show that reduced astrocyte-contact with synapses is dependent on microglial CX3CL1-CX3CR1 signaling and release of Wnts from microglia following whisker removal. These results demonstrate an activity-dependent mechanism by which microglia instruct astrocyte-synapse interactions, which then provides 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 this signaling is upregulated in several disease contexts.