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Opposite regulation of metabotropic glutamate receptor 3 and metabotropic glutamate receptor 5 by inflammatory stimuli in cultured microglia and astrocytes



Opposite regulation of metabotropic glutamate receptor 3 and metabotropic glutamate receptor 5 by inflammatory stimuli in cultured microglia and astrocytes



Neuroscience 205: 29-38



Metabotropic glutamate receptors (mGluRs) were previously shown to modulate several essential functions in glial cells, including cell proliferation, glutamate uptake, neurotrophic support, and inflammatory responses. As these receptors are regularly proposed as promising targets for the treatment of a wide range of neurological disorders, we herein examined the reciprocal modulation of glial mGluRs by inflammation. Such regulation of mGluRs was also studied in cultures from an experimental model of amyotrophic lateral sclerosis (ALS). Indeed, ALS is characterized by increased neuroinflammation, and glial cell cultures derived from the animal model (rat expressing hSOD1(G93A)) show enhanced glial reactivity. Within 72 h, the pro-inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β) induced an increase in mGluR3 and a decrease in mGluR5 gene expression. A similar regulation of these receptors was observed in microglia 48 h after an initial 4-h exposure to lipopolysaccharide. In hSOD1(G93A)-derived glial cultures, the gene up-regulation of mGluR3 (but not the gene down-regulation of mGluR5) was found to be enhanced in both astrocytes and microglia. Together, these results indicate that an inflammatory environment triggers an opposite regulation in the gene expression of the two predominant mGluR subtypes found in glial cells, and that these regulations were particularly robust in hSOD1(G93A) glial cultures. As neuroinflammation commonly occurs in several nervous diseases, its influence on mGluR expression should be taken into account when considering these receptors as future drug targets.

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Accession: 054761231

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PMID: 22245498

DOI: 10.1016/j.neuroscience.2011.12.044


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