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Spatiotemporally selective astrocytic ATP dynamics encode injury information sensed by microglia following brain injury in mice
Nature Neuroscience ( IF 21.2 ) Pub Date : 2024-06-11 , DOI: 10.1038/s41593-024-01680-w
Yue Chen , Pengwei Luan , Juan Liu , Yelan Wei , Chenyu Wang , Rui Wu , Zhaofa Wu , Miao Jing

Injuries to the brain result in tunable cell responses paired with stimulus properties, suggesting the existence of intrinsic processes that encode and transmit injury information; however, the molecular mechanism of injury information encoding is unclear. Here, using ATP fluorescent indicators, we identify injury-evoked spatiotemporally selective ATP dynamics, Inflares, in adult mice of both sexes. Inflares are actively released from astrocytes and act as the internal representations of injury. Inflares encode injury intensity and position at their population level through frequency changes and are further decoded by microglia, driving changes in their activation state. Mismatches between Inflares and injury severity lead to microglia dysfunction and worsening of injury outcome. Blocking Inflares in ischemic stroke in mice reduces secondary damage and improves recovery of function. Our results suggest that astrocytic ATP dynamics encode injury information and are sensed by microglia.



中文翻译:


时空选择性星形胶质细胞 ATP 动力学编码小鼠脑损伤后小胶质细胞感知的损伤信息



大脑损伤会导致可调节的细胞反应与刺激特性相结合,这表明存在编码和传输损伤信息的内在过程;然而,损伤信息编码的分子机制尚不清楚。在这里,我们使用 ATP 荧光指示剂,识别了成年雌性小鼠中损伤诱发的时空选择性 ATP 动力学 Inflares。星形胶质细胞主动释放炎症,充当损伤的内部表征。炎症通过频率变化在其群体水平上编码损伤强度和位置,并由小胶质细胞进一步解码,驱动其激活状态的变化。炎症和损伤严重程度之间的不匹配会导致小胶质细胞功能障碍和损伤结果恶化。阻断小鼠缺血性中风的 Inflares 可减少继发性损伤并改善功能恢复。我们的结果表明星形胶质细胞 ATP 动力学编码损伤信息并被小胶质细胞感知。

更新日期:2024-06-11
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