ATP mediates rapid microglial response to local brain injury in vivo.
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.
Davalos
Dimitrios
D
Molecular Neurobiology Program, Department of Physiology and Neuroscience, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA.
Grutzendler
Jaime
J
Yang
Guang
G
Kim
Jiyun V
JV
Zuo
Yi
Y
Jung
Steffen
S
Littman
Dan R
DR
Dustin
Michael L
ML
Gan
Wen-Biao
WB
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001081:Apyrase / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D017630:Connexins / Q000037:antagonists & inhibitors / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D049452:Green Fluorescent Proteins; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology; D058919:Purinergic P2 Receptor Antagonists; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D017630:Connexins; C546383:P2ry1 protein, mouse; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D049452:Green Fluorescent Proteins; D000255:Adenosine Triphosphate; D001081:Apyrase