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.