Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Cells, Cultured
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Drug Synergism
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Excitatory Amino Acid Agonists / metabolism
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Excitatory Amino Acid Agonists / pharmacology*
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Excitatory Amino Acid Antagonists / metabolism
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Excitatory Amino Acid Antagonists / pharmacology*
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Glutamic Acid / biosynthesis
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Glutamic Acid / metabolism
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Glycine / analogs & derivatives
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Glycine / metabolism
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Glycine / pharmacology
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Ligands
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Lipopolysaccharides / antagonists & inhibitors
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Lipopolysaccharides / pharmacology*
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Microglia / drug effects*
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Microglia / metabolism
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Microglia / physiology*
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Nitrites / antagonists & inhibitors
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Nitrites / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, Metabotropic Glutamate / classification*
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Receptors, Metabotropic Glutamate / metabolism
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Receptors, Metabotropic Glutamate / physiology*
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Resorcinols / metabolism
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Resorcinols / pharmacology
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / biosynthesis
Substances
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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Ligands
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Lipopolysaccharides
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Nitrites
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Receptors, Metabotropic Glutamate
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Resorcinols
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Tumor Necrosis Factor-alpha
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metabotropic glutamate receptor type 1
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Glutamic Acid
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3,5-dihydroxyphenylglycine
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Glycine