Induction of astrogliosis by activated microglia is associated with a down-regulation of metabotropic glutamate receptor 5.
To explore the impact of neuroinflammation on the control of glutamate transmission, we studied the metabotropic glutamate receptor 5 (mGluR5) expression in cultured astrocytes exposed to conditioned medium from lipopolysaccharide-activated microglia. This treatment caused profound changes in astrocyte phenotype that correlated with altered expression of GFAP and vimentin. This putative astrogliosis was accompanied by a down-regulation of mGluR5 protein and mRNA expression, with a maximal effect after 48 h treatment (up to 50% decrease). Such regulation was not observed with medium from naive microglia but was mimicked by direct addition of tumor necrosis factor, a major cytokine released from activated microglia. Conversely, treatment with prostaglandin E2 and induction of nitric oxide production resulted in a significant up-regulation of mGluR5. These results suggest that complex crosstalks between microglia and astrocytes during neuroinflammatory insults would influence glutamate-dependent responses in astrocytes.
Tilleux
Sébastien
S
Laboratoire de Pharmacologie Expérimentale, Université catholique de Louvain, 54.10, Av. Hippocrate 54, 1200 Brussels, Belgium.
Berger
Julie
J
Hermans
Emmanuel
E
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced / Q000503:physiopathology*; D017628:Microglia / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D011134:Polysaccharides; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014746:Vimentin / Q000378:metabolism
D017077:Culture Media, Conditioned; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; C578937:Grm5 protein, rat; D011134:Polysaccharides; D012333:RNA, Messenger; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D014746:Vimentin