Nature Neuroscience8, 752 - 758 (2005)
Published online: 15 May 2005; | doi:10.1038/nn1472
ATP mediates rapid microglial response to local brain injury in vivo
Dimitrios Davalos1, Jaime Grutzendler1, 3, Guang Yang1, Jiyun V Kim2, Yi Zuo1, Steffen Jung2, Dan R Littman2, Michael L Dustin2
& Wen-Biao Gan1
1
Molecular Neurobiology Program, Department of Physiology and Neuroscience, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA.
2
Molecular Pathogenesis Program, Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA.
3
Present address: Northwestern University Department of Neurology, 303 East Chicago Avenue, Chicago, Illinois 60611, USA.
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.
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