C‐Src function is necessary and sufficient for triggering microglial cell activation. Issue 3 (24th November 2014)

• Record Type: Journal Article
• Authors: Socodato, Renato; Portugal, Camila C.; Domith, Ivan; Oliveira, Nádia A.; Coreixas, Vivian S. M.; Loiola, Erick C.; Martins, Tânia; Santiago, Ana Raquel; Paes‐de‐Carvalho, Roberto; Ambrósio, António F.; Relvas, João B.
• Is Part Of: Glia. Volume 63:Issue 3(2015:Mar.)
• Page Start: 497
• Page End: 511
• Publication Date: 2014-11-24
• Subjects: Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.22767
• Languages: English
• ISSNs: 0894-1491

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Microglial cells are the resident macrophages of the central nervous system. Their function is essential for neuronal tissue homeostasis. After inflammatory stimuli, microglial cells become activated changing from a resting and highly ramified cell shape to an amoeboid‐like morphology. These morphological changes are associated with the release of proinflammatory cytokines and glutamate, as well as with high phagocytic activity. The acquisition of such phenotype has been associated with activation of cytoplasmic tyrosine kinases, including those of the Src family (SFKs). In this study, using both <italic>in vivo</italic> and <italic>in vitro</italic> inflammation models coupled to FRET‐based time‐lapse microscopy, lentiviruses‐mediated shRNA delivery and genetic gain‐of‐function experiments, we demonstrate that among SFKs c‐Src function is necessary and sufficient for triggering microglia proinflammatory signature, glutamate release, microglia‐induced neuronal loss, and phagocytosis. c‐Src inhibition in retinal neuroinflammation experimental paradigms consisting of intravitreal injection of LPS or ischemia–reperfusion injury significantly reduced microglia activation changing their morphology to a more resting phenotype and prevented neuronal apoptosis. Our data demonstrate an essential role for c‐Src in microglial cell activation. GLIA 2015;63:497–511</p> </abstract>