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Updated: May 22, 2026

Measurement of Total Calcium in Neurons by Electron Probe X-ray Microanalysis
Published on: November 20, 2013
Long-range Ca2+ waves transmit brain-damage signals to microglia
Dirk Sieger1, Christian Moritz, Thomas Ziegenhals
1EMBL Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany.
Abstract:
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.
Insights
Brain immune cells, microglia, migrate to injury sites via calcium (Ca2+) waves. Glutamate initiates these waves, guiding microglia to clear damaged neurons for tissue repair.
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Microglia, the brain's immune cells, clear injured neurons for tissue regeneration.
- Understanding how death signals spatially and temporally guide microglia to injury sites is crucial.
Purpose of the Study:
- To investigate the real-time mechanisms controlling microglial migration to neuronal injury sites.
- To identify signaling molecules and pathways involved in microglial response to cell death.
Main Methods:
- Utilized the optically transparent zebrafish larval brain for real-time imaging.
- Analyzed calcium (Ca2+) waves and their role in microglial responses.
- Investigated the involvement of ATP and glutamate in the signaling cascade.
Main Results:
- Identified rapidly propagating Ca2+ waves that dictate the extent of microglial response to neuronal death.
- Demonstrated that Ca2+-mediated microglial responses depend on ATP, but Ca2+ wave propagation is ATP-independent.
- Identified glutamate as a key inducer of Ca2+-transmitted microglial attraction.
Conclusions:
- A novel mechanism for microglial-targeted migration to neuronal injuries has been revealed.
- This process is initiated by glutamate and propagates as a Ca2+ wave across the brain.
- This finding provides insights into brain repair and regeneration processes.
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