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Two-photon Imaging of Microglial Processes' Attraction Toward ATP or Serotonin in Acute Brain Slices
Published on: January 31, 2019
ATP mediates rapid microglial response to local brain injury in vivo
Dimitrios Davalos1, Jaime Grutzendler, Guang Yang
1Molecular Neurobiology Program, Department of Physiology and Neuroscience, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA.
Abstract:
Parenchymal microglia are the principal immune cells of the brain. Time-lapse two-photon imaging of GFP-labeled microglia demonstrates that the fine termini of microglial processes are highly dynamic in the intact mouse cortex. Upon traumatic brain injury, microglial processes rapidly and autonomously converge on the site of injury without cell body movement, establishing a potential barrier between the healthy and injured tissue. This rapid chemotactic response can be mimicked by local injection of ATP and can be inhibited by the ATP-hydrolyzing enzyme apyrase or by blockers of G protein-coupled purinergic receptors and connexin channels, which are highly expressed in astrocytes. The baseline motility of microglial processes is also reduced significantly in the presence of apyrase and connexin channel inhibitors. Thus, extracellular ATP regulates microglial branch dynamics in the intact brain, and its release from the damaged tissue and surrounding astrocytes mediates a rapid microglial response towards injury.
Insights
Brain microglia exhibit dynamic processes that rapidly migrate to injury sites, guided by extracellular ATP released from damaged tissue and astrocytes. This ATP signaling regulates microglial branch dynamics and injury response.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are the primary immune cells in the brain parenchyma.
- Microglial process dynamics are crucial for brain surveillance and response.
Purpose of the Study:
- To investigate the role of extracellular ATP in regulating microglial process dynamics and their response to traumatic brain injury.
- To elucidate the signaling pathways involved in microglial chemotaxis towards injury sites.
Main Methods:
- Time-lapse two-photon imaging of GFP-labeled microglia in the intact and injured mouse cortex.
- Local injection of ATP to mimic injury.
- Inhibition studies using apyrase and blockers of purinergic receptors and connexin channels.
Main Results:
- Microglial processes are highly dynamic in the intact cortex.
- Following traumatic brain injury, microglial processes rapidly converge on the injury site without cell body translocation.
- This response is mediated by extracellular ATP and involves purinergic receptors and connexin channels.
- Apyrase and channel inhibitors significantly reduced baseline microglial process motility and injury response.
Conclusions:
- Extracellular ATP is a key regulator of microglial branch dynamics in the healthy brain.
- ATP released from damaged tissue and astrocytes mediates the rapid microglial chemotactic response to injury.
- Microglial process dynamics and directed migration are essential for establishing a barrier at injury sites.
