Long-range Ca2+ waves transmit brain-damage signals to microglia.
Microglia are the resident phagocytes of the brain that are responsible for the clearance of injured neurons, an essential step in subsequent tissue regeneration. How death signals are controlled both in space and time to attract these cells toward the site of injury is a topic of great interest. To this aim, we have used the optically transparent zebrafish larval brain and identified rapidly propagating Ca2+ waves that determine the range of microglial responses to neuronal cell death. We show that while Ca2+-mediated microglial responses require ATP, the spreading of intercellular Ca2+ waves is ATP independent. Finally, we identify glutamate as a potent inducer of Ca2+-transmitted microglial attraction. Thus, this real-time analysis reveals the existence of a mechanism controlling microglial targeted migration to neuronal injuries that is initiated by glutamate and proceeds across the brain in the form of a Ca2+ wave.
EMBL Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany.
Dirk
D
Sieger
Christian
C
Moritz
Thomas
T
Ziegenhals
Sergey
S
Prykhozhij
Francesca
F
Peri
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002614:Chelating Agents / Q000378:metabolism; D018698:Glutamic Acid / Q000502:physiology; D053685:Laser Therapy; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D015027:Zebrafish / Q000254:growth & development / Q000502:physiology
D002614:Chelating Agents; D018698:Glutamic Acid; D000255:Adenosine Triphosphate