Activation of microglial G‑protein-coupled receptor 30 protects neurons against excitotoxicity through NF-κB/MAPK

Liu-Kun Yang1, Liang Lu1, Jiao Yue2

  • 1Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China.

Insights

Activating microglial G-protein-coupled receptor 30 (GPR30) protects neurons from excitotoxicity by modulating microglial responses. This finding highlights microglial GPR30 as a potential therapeutic target for neurodegenerative diseases.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Neuroexcitotoxicity contributes to neuronal damage and neurodegenerative diseases.
  • Neuronal and astrocytic G-protein-coupled receptor 30 (GPR30) show neuroprotective effects.
  • The role of GPR30 in microglia during neuroexcitotoxicity is not well understood.

Purpose of the Study:

  • To investigate the function of microglial GPR30 in neuroprotection against glutamate-induced excitotoxicity.
  • To determine the effects of GPR30 activation on microglial behavior and inflammatory polarization.

Main Methods:

  • N9 microglial cells were treated with glutamate and a GPR30 agonist (G1).
  • Assays included MTT, Western blot, immunocytochemistry, phagocytosis, and wound healing.
  • Co-culture experiments with neurons and microglia were performed.

Main Results:

  • GPR30 activation by G1 inhibited glutamate-induced microglial proliferation and activation.
  • G1 treatment promoted M2 microglial polarization and reduced M1 polarization.
  • Microglial GPR30 activation protected neurons from excitotoxicity via NF-κB/MAPK signaling pathways.

Conclusions:

  • Microglial GPR30 plays a crucial role in neuroprotection against excitotoxicity.
  • Targeting microglial GPR30 may offer a therapeutic strategy for neurodegenerative conditions.
  • GPR30 modulates microglial polarization and inflammatory responses relevant to neuronal health.

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