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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine Triphosphate / antagonists & inhibitors
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Adenosine Triphosphate / metabolism*
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Animals
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Apyrase / pharmacology
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Astrocytes / drug effects
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Astrocytes / metabolism
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Brain / metabolism
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Brain / pathology
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Brain / physiopathology
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Brain Injuries / metabolism*
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Brain Injuries / pathology
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Brain Injuries / physiopathology
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Cell Communication / drug effects
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Cell Communication / physiology
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Chemotaxis / drug effects
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Chemotaxis / physiology*
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Connexins / antagonists & inhibitors
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Connexins / metabolism
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Gliosis / metabolism*
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Gliosis / pathology
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Gliosis / physiopathology
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Green Fluorescent Proteins
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Mice
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Mice, Transgenic
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Microglia / cytology
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Microglia / drug effects
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Microglia / metabolism*
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Phagocytosis / physiology
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Purinergic P2 Receptor Antagonists
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Reaction Time / drug effects
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Reaction Time / physiology
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Receptors, Purinergic P2 / metabolism*
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Receptors, Purinergic P2Y1
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Signal Transduction / drug effects
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Signal Transduction / physiology
Substances
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Connexins
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P2ry1 protein, mouse
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Purinergic P2 Receptor Antagonists
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Receptors, Purinergic P2
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Receptors, Purinergic P2Y1
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Green Fluorescent Proteins
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Adenosine Triphosphate
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Apyrase