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Evidence Group I mGluR Drugs Modulate the Activation Profile of Lipopolysaccharide-Exposed Microglia in Culture

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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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Acknowledgments

Supported in part by a Program Grant from the NH&MRC (Australia) of which PMB is a Research Fellow.

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Authors and Affiliations

  1. Molecular Neuropharmacology, Florey Neuroscience Institute, University of Melbourne, Parkville, VIC, 3010, Australia

    Mark C. Farso, Ross D. O’Shea & Philip M. Beart

  2. Department of Neuroscience, Douglas Mental Health University Institute, 6875 LaSalle Blvd, Montréal, QC, H4H 1R3, Canada

    Mark C. Farso

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  1. Mark C. Farso
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Correspondence to Mark C. Farso.

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Farso, M.C., O’Shea, R.D. & Beart, P.M. Evidence Group I mGluR Drugs Modulate the Activation Profile of Lipopolysaccharide-Exposed Microglia in Culture. Neurochem Res 34, 1721–1728 (2009). https://doi.org/10.1007/s11064-009-9999-3

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  • DOI: https://doi.org/10.1007/s11064-009-9999-3

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