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A self-propelling cycle mediated by reactive oxide species and nitric oxide exists in LPS-activated microglia

Zhang Lijia1, Siqi Zhao, Xiaoxiao Wang

  • 1Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.

Neurochemistry International
|September 25, 2012
PubMed

Insights

Microglia activation in neurodegeneration may involve a self-propelling cycle. Lipopolysaccharide (LPS) triggers microglia to release reactive oxygen species (ROS) and nitric oxide (NO), which can perpetuate inflammation and neuron damage.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia, the brain's immune cells, are implicated in neurodegenerative diseases through chronic activation.
  • Reactive microgliosis, a cycle of microglial activation and neuron damage, is thought to drive disease progression.

Purpose of the Study:

  • To investigate the potential self-perpetuating mechanisms of microglial activation.
  • To explore the roles of intracellular reactive oxygen species (iROS) and nitric oxide (NO) in microglial activation.

Main Methods:

  • Stimulation of N9 microglia with lipopolysaccharide (LPS).
  • Measurement of nitric oxide (NO) and intracellular reactive oxygen species (iROS) levels.
  • Assessment of primary cortical neuron viability.
  • Intervention with antioxidants (NAC) and NADPH oxidase inhibitors (DPI), and use of gp91phox siRNA.

Main Results:

  • LPS induced sustained microglial activation and NO production.
  • Activated microglia culture medium reduced neuron viability, an effect blocked by NAC and DPI.
  • LPS increased iROS, preceding NO production via iNOS.
  • NO further increased iROS production in microglia.
  • gp91phox siRNA reversed iROS increase.

Conclusions:

  • A self-propelling cycle involving iROS and NO may sustain microglial activation after LPS exposure.
  • This cycle could contribute to ongoing neuroinflammation and the progression of neurodegenerative diseases.

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