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Updated: Nov 9, 2025

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
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.
Abstract:
Neuroexcitotoxicity is a common feature in neuronal damage and neurodegenerative diseases. Our previous studies have confirmed that neuronal and astrocytic G‑protein-coupled receptor 30 (GPR30) play a key role in neuroprotection in vivo and in vitro. Microglia are considered as immune cells in the central nervous system. However, the role of microglial GPR30 in neuroprotection against neuroexcitotoxicity remained unclear. In this study, MTT, Western blot, immunocytochemical staining, phagocytosis assay and wound healing assay were employed to detect the effect of GPR30 in N9 microglial cells after exposure to glutamate. We found that the treatment of GPR30 specific agonist G1 inhibited glutamate-induced proliferation and activation in N9 microglial cells. G1 inhibited M1 polarization, facilitated M2 polarization, and decreased over-phagocytosis but had no effect on migration ability in microglia. The result of neurons and microglia co-culture showed that the activation of microglial GPR30 protected neurons from excitotoxicity through the NF-κB/MAPK signaling pathways. Our findings suggested a key role of microglial GPR30 in excitatory neuronal damage and neurodegenerative diseases.
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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