Evidence group I mGluR drugs modulate the activation profile of lipopolysaccharide-exposed microglia in culture.
Metabotropic glutamate receptors (mGluRs) may play a role in modulating microglial activation, but group I mGluRs have received little attention. This study aimed to investigate the effects of group I mGluR selective ligands, (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) and (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA), in lipopolysaccharide (LPS; 50 ng/ml)-activated rat microglial cultures. (S)-3,5-DHPG (150 microM) significantly reduced (approximately 20-60%) the LPS-mediated production of nitrite (NO2(-)), tumour necrosis factor alpha (TNF-alpha), and L-glutamate (Glu) at 24 and 72 h. Image analysis revealed increases in both cell area and number, with larger amoeboid microglia (with retracted processes) formed following 2 h LPS exposure. This cellular population was absent after addition of (S)-3,5-DHPG, an effect antagonised by AIDA, and a concomitant reduction in cell area was also found. Taken together, these biochemical and morphological observations suggest that (S)-3,5-DHPG reduces microglial activation, indicating a role for group I mGluRs in modulating microglial function.
Farso
Mark C
MC
Molecular Neuropharmacology, Florey Neuroscience Institute, University of Melbourne, Parkville, VIC 3010, Australia. mfarso@gmail.com
O'Shea
Ross D
RD
Beart
Philip M
PM
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004357:Drug Synergism; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000494:pharmacology*; D018698:Glutamic Acid / Q000096:biosynthesis / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D009573:Nitrites / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000145:classification* / Q000378:metabolism / Q000502:physiology*; D012118:Resorcinols / Q000378:metabolism / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D008024:Ligands; D008070:Lipopolysaccharides; D009573:Nitrites; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; D014409:Tumor Necrosis Factor-alpha; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid; C079215:3,5-dihydroxyphenylglycine; D005998:Glycine