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Reduced connexin43 expression correlates with c‐Src activation, proliferation, and glucose uptake in reactive astrocytes after an excitotoxic insult
Author(s) -
Gangoso Ester,
Ezan Pascal,
ValleCasuso José Carlos,
HerreroGonzález Sandra,
Koulakoff Annette,
Medina Jose M.,
Giaume Christian,
Tabernero Arantxa
Publication year - 2012
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.22418
Subject(s) - biology , glial fibrillary acidic protein , downregulation and upregulation , proto oncogene tyrosine protein kinase src , microbiology and biotechnology , astrogliosis , astrocyte , neuroglia , reactive oxygen species , glucose uptake , signal transduction , endocrinology , biochemistry , immunology , central nervous system , immunohistochemistry , insulin , gene
Abstract In diverse brain pathologies, astrocytes become reactive and undergo profound phenotypic changes. Connexin43 (Cx43), the main gap junction channel‐forming protein in astrocytes, is one of the proteins modified in reactive astrocytes. Downregulation of Cx43 in cultured astrocytes activates c‐Src, promotes proliferation, and increases the rate of glucose uptake; however, so far there have been no studies examining whether this cascade of events takes place in reactive astrocytes. In this work, we analyzed this pathway after a cortical lesion induced by a kainic acid injection. As previously described, astrocytes reacted to the lesion with an increase in glial fibrillary acidic protein and a decrease in Cx43 expression. Some of these reactive astrocytes proliferated, as estimated by bromodeoxyuridine incorporation and cyclins D1 and D3 upregulation. In addition, the expression of the glucose transporter GLUT‐3 and the enzyme responsible for glucose phosphorylation, Type II hexokinase (Hx‐2), were induced in reactive astrocytes, suggesting an increased glucose uptake. Previous in vitro studies reported that c‐Src is the link between Cx43 and glucose uptake and proliferation in astrocytes. Here, we found that c‐Src activity increased in the lesioned area. c‐Src activation and Cx43 downregulation preceded the peak of Hx‐2 and cyclin D3 expression, suggesting that c‐Src could mediate the effect of Cx43 on glucose uptake and proliferation in reactive astrocytes after an excitotoxic insult. Interestingly, we identify c‐Src, GLUT‐3, and Hx‐2 in the signaling mechanisms involved in the reaction of astroglia to injury. Altogether these data contribute to identify new therapeutical targets to enhance astrocyte neuroprotective activities. © 2012 Wiley Periodicals, Inc.