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  3. Spatiotemporally selective astrocytic ATP dynamics encode injury information sensed by microglia following brain injury in mice

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

  • Nat Neurosci. 2024 Jun 11. doi: 10.1038/s41593-024-01680-w.
Yue Chen # 1,  Pengwei Luan # 1 2,  Juan Liu # 1 2,  Yelan Wei 1 3,  Chenyu Wang 1 4,  Rui Wu 1 5,  Zhaofa Wu 6 7 8,  Miao Jing 9
Affiliations

Affiliations

  • 1 Chinese Institute for Brain Research, Beijing, China.
  • 2 Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
  • 3 Department of College of Physical Education and Sport, Beijing Normal University, Beijing, China.
  • 4 Capital Medical University, Basic Medical Sciences, Beijing, China.
  • 5 China Agricultural University, Beijing, China.
  • 6 State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China.
  • 7 PKU-IDG/McGovern Institute for Brain Research, Beijing, China.
  • 8 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
  • 9 Chinese Institute for Brain Research, Beijing, China. jingmiao@cibr.ac.cn.
  • # Contributed equally.
PMID: 38862791 DOI: 10.1038/s41593-024-01680-w
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.

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