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Morphine preconditioning reduces lipopolysaccharide and interferon-gamma-induced mouse microglial cell injury via

M-S Gwak1, L Li, Z Zuo

  • 1Department of Anesthesiology, University of Virginia Health System, University of Virginia, 1 Hospital Drive, Charlottesville, VA 22908-0710, USA; Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Kangnam-Ku, Seoul, 135-710, Korea.

Neuroscience
|February 17, 2010
PubMed

Insights

Morphine preconditioning protects microglial cells from inflammatory injury. This protective effect is mediated by delta 1 opioid receptors, not by inhibiting inducible nitric oxide synthase.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Microglial cells are crucial in brain inflammation for diseases like stroke and neurodegeneration.
  • Limited knowledge exists on protecting microglial cells from inflammatory damage.

Purpose of the Study:

  • To investigate the protective effects of morphine preconditioning on microglial cells.
  • To identify the specific opioid receptor subtypes involved in morphine's protective mechanism.

Main Methods:

  • C8-B4 mouse microglial cells were exposed to lipopolysaccharide (LPS) plus interferon-gamma (IFN-γ) to induce cytotoxicity.
  • Cells were preconditioned with varying concentrations of morphine.
  • The involvement of opioid receptor antagonists (naloxone, naltrindole, 7-benzylidenenaltrexone maleate, beta-funaltrexamine, nor-binaltorphimine, naltriben) was assessed.
  • Inducible nitric oxide synthase (iNOS) expression was measured.

Main Results:

  • Morphine preconditioning significantly reduced LPS plus IFN-γ-induced microglial cell injury in a dose-dependent manner.
  • The protective effect was blocked by naloxone, naltrindole, and 7-benzylidenenaltrexone maleate, indicating involvement of delta opioid receptors, particularly delta 1.
  • The protective effect was not affected by antagonists for mu, kappa, or delta 2 opioid receptors.
  • Morphine preconditioning did not alter the expression of inducible nitric oxide synthase (iNOS).

Conclusions:

  • Morphine exhibits a preconditioning effect, protecting microglial cells against inflammatory insults.
  • This neuroprotection is primarily mediated through delta 1 opioid receptors.
  • The protective mechanism does not involve the inhibition of inducible nitric oxide synthase (iNOS).

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