Related Experiment Video

Updated: May 18, 2026

Primary Microglia Isolation from Mixed Glial Cell Cultures of Neonatal Rat Brain Tissue
10:20

Primary Microglia Isolation from Mixed Glial Cell Cultures of Neonatal Rat Brain Tissue

Published on: August 15, 2012

39.7K

Metabotropic Glutamate Receptor 8 Suppresses M1 Polarization in Microglia by Alleviating Endoplasmic Reticulum Stress

Yangzhi Xie1, Liang Chen1, Jiacheng Chen2

  • 1Department of Neurology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China.

Journal of Integrative Neuroscience
|February 29, 2024
PubMed
Abstract

Insights

Metabotropic glutamate receptor 8 (GRM8) activation reduces neuroinflammation by decreasing endoplasmic reticulum (ER) stress and restoring mitochondrial function. This suggests GRM8 is a potential therapeutic target for neurodegenerative diseases.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia-driven neuroinflammation is central to neurodegeneration.
  • Metabotropic glutamate receptor 8 (GRM8) supports neuronal survival but its role in neuroinflammation is unknown.
  • Endoplasmic reticulum (ER) stress and mitochondrial dysfunction from calcium overload trigger neuroinflammation.

Purpose of the Study:

  • Investigate GRM8's anti-inflammatory effects in microglia.
  • Determine GRM8's role in mitigating ER stress and mitochondrial dysfunction.
  • Explore GRM8's impact on calcium signaling pathways.

Main Methods:

  • BV2 microglial cells were treated with a GRM8 agonist before lipopolysaccharide exposure.
  • Assessed pro-inflammatory cytokines, microglial polarization, and neuronal viability.
  • Quantified cAMP, inositol-1,4,5-triphosphate receptor (IP3R)-dependent calcium release, ER calcium, mitochondrial function, ER stress markers, and NF-κB activation.

Main Results:

  • GRM8 activation suppressed pro-inflammatory cytokines and promoted an anti-inflammatory microglial phenotype.
  • GRM8 enhanced survival of co-cultured neuron-like PC12 cells.
  • GRM8 inhibited cAMP, desensitized IP3R, reduced calcium release, restored mitochondrial function, attenuated ER stress, and deactivated NF-κB signaling.

Conclusions:

  • GRM8 activation protects against neuroinflammation by reducing ER stress and mitochondrial dysfunction.
  • IP3R-mediated calcium signaling is crucial for GRM8's protective effects.
  • GRM8 represents a promising therapeutic target for neuroinflammation.
Keywords:
M1/M2 polarizationendoplasmic reticulum stressmetabotropic glutamate receptor 8mitochondrial functionneuroinflammation

More Related Videos

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates09:12

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates

Published on: January 30, 2014

15.9K
Magnetic Isolation of Microglial Cells from Neonate Mouse for Primary Cell Cultures07:23

Magnetic Isolation of Microglial Cells from Neonate Mouse for Primary Cell Cultures

Published on: July 25, 2022

3.0K

Related Concept Videos

Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
Cholinergic Receptors: Muscarinic01:25

Cholinergic Receptors: Muscarinic

The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine. 
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+. Activation...
Direct-Acting Cholinergic Agonists: Pharmacological Actions00:59

Direct-Acting Cholinergic Agonists: Pharmacological Actions

Direct-acting cholinergic agonists exert their pharmacological actions by mimicking the effects of acetylcholine on postsynaptic muscarinic receptors to generate parasympathetic responses. These agents elicit a range of physiological responses, including cardiovascular effects. For example, activation of muscarinic receptors induces bradycardia, decreased cardiac output, reduced peripheral resistance, and consequent hypotension. In the eye, stimulation of M3 receptors leads to smooth muscle...
Direct-Acting Cholinergic Agonists: Therapeutic Uses01:11

Direct-Acting Cholinergic Agonists: Therapeutic Uses

Direct-acting cholinergic agonists have many therapeutic uses in various medical fields. Choline esters, including acetylcholine, have limited clinical utility due to their non-selectivity and short duration of action. Still, acetylcholine and carbachol are applied topically during ophthalmologic surgery to induce miosis. Pilocarpine, a muscarinic and ganglionic stimulator, effectively treats open-angle glaucoma and alleviates xerostomia and dry mouth caused by radiotherapy or Sjögren syndrome.
Cholinergic Antagonists: Pharmacological Actions01:28

Cholinergic Antagonists: Pharmacological Actions

Antimuscarinic drugs block muscarinic receptors in multiple systems, including the gut, eye, smooth muscles, respiratory tract, cardiovascular, and central nervous systems. They produce similar effects with varying selectivity depending on the specific agent and tissue. Here are the key pharmacological actions of antimuscarinics:
Gastrointestinal Effects: Antimuscarinics reduce gut contractions, increase gastric emptying, and slow intestinal transit. They partly inhibit gastric acid secretion...
Open Angle Glaucoma: Treatment01:27

Open Angle Glaucoma: Treatment

In open-angle glaucoma, the iridocorneal angle remains open, but the trabecular meshwork becomes stiff, slowing down the outflow of aqueous humor. This causes a buildup of aqueous humor in the anterior chamber, leading to a sudden increase in intraocular pressure. The treatment for open-angle glaucoma focuses on reducing the elevated intraocular pressure by either decreasing the secretion of aqueous humor or increasing its outflow.
Drugs such as carbonic anhydrase inhibitors, α2- and...