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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.

Original publication

DOI

10.1038/nn1472

Type

Journal article

Journal

Nat Neurosci

Publication Date

06/2005

Volume

8

Pages

752 - 758

Keywords

Adenosine Triphosphate, Animals, Apyrase, Astrocytes, Brain, Brain Injuries, Cell Communication, Chemotaxis, Connexins, Gliosis, Green Fluorescent Proteins, Mice, Mice, Transgenic, Microglia, Phagocytosis, Purinergic P2 Receptor Antagonists, Reaction Time, Receptors, Purinergic P2, Receptors, Purinergic P2Y1, Signal Transduction