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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
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Opioid receptor activation suppresses the neuroinflammatory response by promoting microglial M2 polarization

Akash S Mali1, Jiri Novotny1

  • 1Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic.

Molecular and Cellular Neurosciences
|June 6, 2022
PubMed

Insights

Opioid agonists shift microglia from a pro-inflammatory (M1) to an anti-inflammatory (M2) state, reducing neuroinflammation. This modulation via the TREM2/NF-κB pathway suggests potential therapeutic benefits for neurodegenerative diseases.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Microglial activation is central to neuroinflammation.
  • Microglia exhibit pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes.
  • The role of opioid receptors (ORs) in microglial function is largely unexplored.

Purpose of the Study:

  • To investigate the impact of OR agonists on microglial polarization.
  • To determine if opioids can modulate M1/M2 phenotypes in microglia.
  • To elucidate the signaling pathways involved in opioid-mediated microglial regulation.

Main Methods:

  • Utilized C8-B4 microglial cell line.
  • Administered OR agonists (DAMGO, DADLE, U-50488) and lipopolysaccharide (LPS).
  • Assessed microglial polarization markers, phagocytic activity, migration, and signaling pathways (TREM2/NF-κB).

Main Results:

  • Opioids suppressed LPS-induced M1 polarization.
  • Opioids promoted M2 polarization, indicated by increased IL-4, IL-10, arginase 1, and CD 206.
  • Opioid effects were mediated through the TREM2/NF-κB signaling pathway.

Conclusions:

  • Opioid receptor agonists can effectively modulate microglial polarization towards an anti-inflammatory phenotype.
  • This modulation involves the TREM2/NF-κB signaling pathway.
  • Opioids exhibit potential anti-inflammatory and neuroprotective effects, relevant for neurodegenerative disease therapies.
Keywords:
LipopolysaccharideMicrogliaNF-κBNeuroinflammationOpioidsTREM2

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