北京脑科学与类脑研究所井淼研究团队在研究中取得进展。他们发现时空选择性星形细胞ATP动态编码小鼠脑损伤后小胶质细胞感知的损伤信息。相关论文于2024年6月11日发表在《自然—神经科学》杂志上。

据介绍，脑损伤会引发与刺激特性相匹配的可调细胞反应，这表明存在内在过程来编码和传递损伤信息。然而，损伤信息编码的分子机制尚不清楚。

使用ATP荧光指示剂，在雄性和雌性成年小鼠中鉴定出由损伤引发的时空选择性ATP动态，称为Inflares。Inflares是从星形胶质细胞主动释放的，作为损伤的内部表征。Inflares通过频率变化在其群体水平上编码损伤的强度和位置，并进一步被小胶质细胞解码，驱动其激活状态的变化。

Inflares与损伤严重程度的不匹配会导致小胶质细胞功能障碍并加剧损伤结果。在小鼠的缺血性中风中阻断Inflares可以减少二次损伤并改善功能恢复。他们的研究结果表明，星形胶质细胞的ATP动态编码损伤信息，并被小胶质细胞感知。

附：英文原文

Title: Spatiotemporally selective astrocytic ATP dynamics encode injury information sensed by microglia following brain injury in mice

Author: Chen, Yue, Luan, Pengwei, Liu, Juan, Wei, Yelan, Wang, Chenyu, Wu, Rui, Wu, Zhaofa, Jing, Miao

Issue&Volume: 2024-06-11

Abstract: 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. The mechanisms regulating microglial response to brain injury are unclear. Here, the authors show that astrocytic ATP dynamics encode injury information and trigger microglia response affecting the tissue damage and recovery of function following injury in mice.

DOI: 10.1038/s41593-024-01680-w

Source: https://www.nature.com/articles/s41593-024-01680-w