†These authors contributed equally.
Background: Microglia-mediated neuroinflammation is a hallmark of
neurodegeneration. Metabotropic glutamate receptor 8 (GRM8) has been reported to
promote neuronal survival in neurodegenerative diseases, yet the effect of GRM8
on neuroinflammation is still unclear. Calcium overload-induced endoplasmic
reticulum (ER)-mitochondrial miscommunication has been reported to trigger
neuroinflammation in the brain. The aim of this study was to investigate putative
anti-inflammatory effects of GRM8 in microglia, specifically focusing on its role
in calcium overload-induced ER stress and mitochondrial dysfunction.
Methods: BV2 microglial cells were pretreated with GRM8 agonist prior to
lipopolysaccharide administration. Pro-inflammatory cytokine levels and the
microglial polarization state in BV2 cells were then quantified. Cellular
apoptosis and the viability of neuron-like PC12 cells co-cultured with BV2 cells
were examined using flow cytometry and a Cell Counting Kit-8, respectively. The
concentration of cAMP, inositol-1,4,5-triphosphate receptor (IP3R)-dependent
calcium release, ER Ca