Evidence Group I mGluR Drugs Modulate the Activation Profile of Lipopolysaccharide-Exposed Microglia in Culture |
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Authors: | Mark C Farso Ross D O’Shea Philip M Beart |
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Institution: | (1) Molecular Neuropharmacology, Florey Neuroscience Institute, University of Melbourne, Parkville, VIC, 3010, Australia;(2) Department of Neuroscience, Douglas Mental Health University Institute, 6875 LaSalle Blvd, Montréal, QC, H4H 1R3, Canada |
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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 μM) significantly reduced (approximately 20–60%) the LPS-mediated production of nitrite (NO2
−), tumour necrosis factor alpha (TNF-α), 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. |
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Keywords: | Microglia LPS Group I mGluR (S)-3 5-DHPG Anti-inflammatory |
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