z-logo
Premium
Systemic inflammation regulates microglial responses to tissue damage in vivo
Author(s) -
Gyoneva Stefka,
Davalos Dimitrios,
Biswas Dipankar,
Swanger Sharon A.,
GarnierAmblard Ethel,
Loth Francis,
Akassoglou Katerina,
Traynelis Stephen F.
Publication year - 2014
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22686
Subject(s) - microglia , neuroinflammation , inflammation , in vivo , biology , adenosine a2a receptor , neuroglia , receptor , proinflammatory cytokine , lipopolysaccharide , neuroscience , microbiology and biotechnology , immunology , adenosine receptor , central nervous system , agonist , biochemistry
Microglia, the resident immune cells of the central nervous system, exist in either a “resting” state associated with physiological tissue surveillance or an “activated” state in neuroinflammation. We recently showed that ATP is the primary chemoattractor to tissue damage in vivo and elicits opposite effects on the motility of activated microglia in vitro through activation of adenosine A 2A receptors. However, whether systemic inflammation affects microglial responses to tissue damage in vivo remains largely unknown. Using in vivo two‐photon imaging of mice, we show that injection of lipopolysaccharide (LPS) at levels that can produce both clear neuroinflammation and some features of sepsis significantly reduced the rate of microglial response to laser‐induced ablation injury in vivo . Under proinflammatory conditions, microglial processes initially retracted from the ablation site, but subsequently moved toward and engulfed the damaged area. Analyzing the process dynamics in 3D cultures of primary microglia indicated that only A 2A , but not A 1 or A 3 receptors, mediate process retraction in LPS‐activated microglia. The A 2A receptor antagonists caffeine and preladenant reduced adenosine‐mediated process retraction in activated microglia in vitro . Finally, administration of preladenant before induction of laser ablation in vivo accelerated the microglial response to injury following systemic inflammation. The regulation of rapid microglial responses to sites of injury by A 2A receptors could have implications for their ability to respond to the neuronal death occurring under conditions of neuroinflammation in neurodegenerative disorders. GLIA 2014;62:1345–1360

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here