Purines induce directed migration and rapid homing of microglia to injured pyramidal neurons in developing hippocampus

Dana Kurpius; Eric P Nolley; Michael E Dailey

doi:10.1002/glia.20509

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Purines induce directed migration and rapid homing of microglia to injured pyramidal neurons in developing hippocampus

Journal article

Peer reviewed

Purines induce directed migration and rapid homing of microglia to injured pyramidal neurons in developing hippocampus

Dana Kurpius, Eric P Nolley and Michael E Dailey

Glia, Vol.55(8), pp.873-884

06/2007

DOI: 10.1002/glia.20509

PMID: 17405148

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Abstract

Traumatic CNS injury activates and mobilizes resident parenchymal microglia (MG), which rapidly accumulate near injured neurons where they transform into phagocytes. The mechanisms underlying this rapid 'homing' in situ are unknown. Using time-lapse confocal imaging in acutely excised neonatal hippocampal slices, we show that rapid accumulation of MG near somata of injured pyramidal neurons in the stratum pyramidale (SP) results from directed migration from tissue regions immediately adjacent to (<200 microm from) the SP. Time-lapse sequences also reveal a 'spreading activation wave' wherein MG situated progressively farther from the SP begin to migrate later and exhibit less directional migration toward the SP. Because purines have been implicated in MG activation and chemotaxis, we tested whether ATP/ADP released from injured pyramidal neurons might account for these patterns of MG behavior. Indeed, application of apyrase, which degrades extracellular ATP/ADP, inhibits MG motility and homing to injured neurons in the SP. Moreover, bath application of exogenous ATP/ADP disrupts MG homing by inducing directional migration toward the slice exterior and away from injured neurons. These results indicate that extracellular ATP/ADP is both necessary and sufficient to induce directional migration and rapid homing of neonatal MG to injured neurons in situ. Rapid, ATP/ADP-dependent MG homing may promote clearance of dead and dying cells and help limit secondary damage during the critical first few hours after neuronal injury.

Cell Communication - immunology

Cell Count

Adenosine Triphosphate - pharmacology

Cell Movement - immunology

Microglia - immunology

Brain Injuries - immunology

Apyrase - pharmacology

Adenosine Triphosphate - metabolism

Hippocampus - growth & development

Organ Culture Techniques

Animals, Newborn

Microglia - cytology

Hippocampus - immunology

Mice, Inbred C57BL

Phagocytosis - immunology

Rats

Hippocampus - pathology

Pyramidal Cells - injuries

Rats, Sprague-Dawley

Adenosine Diphosphate - pharmacology

Cell Movement - drug effects

Microscopy, Confocal

Animals

Cell Communication - drug effects

Pyramidal Cells - pathology

Mice

Adenosine Diphosphate - metabolism

Brain Injuries - pathology

Details

Title: Subtitle: Purines induce directed migration and rapid homing of microglia to injured pyramidal neurons in developing hippocampus
Creators: Dana Kurpius - Department of Biological Sciences, The University of Iowa, Iowa City, Iowa 52242-1324, USA
Eric P Nolley
Michael E Dailey
Resource Type: Journal article
Publication Details: Glia, Vol.55(8), pp.873-884
Publisher: United States
DOI: 10.1002/glia.20509
PMID: 17405148
ISSN: 0894-1491
eISSN: 1098-1136
Grant note: S10 RR017941 / NCRR NIH HHS R01 NS043468 / NINDS NIH HHS NS43468 / NINDS NIH HHS
Language: English
Date published: 06/2007
Academic Unit: Iowa Neuroscience Institute; Biology
Record Identifier: 9984070450702771

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