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Updated: Jul 4, 2026

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
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Zinc triggers microglial activation.

Tiina M Kauppinen1, Youichirou Higashi, Sang Won Suh

  • 1Department of Neurology, University of California, Veterans Affairs Medical Center, San Francisco, California 94121, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|May 30, 2008
PubMed
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This summary is machine-generated.

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Extracellular zinc directly activates microglia, the brain's immune cells, by triggering a signaling pathway involving NADPH oxidase, PARP-1, and NF-kappaB, contributing to neurological disorders.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia are the primary immune cells in the central nervous system (CNS).
  • Microglial activation, characterized by morphological changes and release of inflammatory factors, can contribute to neuronal damage.
  • Zinc is released during conditions associated with microglial activation, and its chelation can mitigate neuronal death in neurological disease models.

Purpose of the Study:

  • To investigate whether extracellular zinc directly triggers microglial activation.
  • To elucidate the signaling pathway involved in zinc-induced microglial activation.
  • To determine the role of zinc in microglial responses during neurological conditions like ischemia-reperfusion.

Main Methods:

  • Utilized NF-kappaB reporter gene assays in transfected microglia.

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  • Assessed nitric oxide production, F4/80 expression, and cytokine profiles in zinc-exposed microglia.
  • Employed genetic knockout models (PARP-1, NADPH oxidase deficient mice) and in vivo zinc injection.
  • Investigated microglial activation following cerebral ischemia-reperfusion and the effect of zinc chelation.
  • Main Results:

    • Zinc exposure significantly increased NF-kappaB activity, nitric oxide production, and F4/80 expression in microglia.
    • Zinc-induced microglial activation was dependent on NADPH oxidase, PARP-1, and NF-kappaB activation.
    • In vivo, zinc injection and ischemia-reperfusion-induced zinc release triggered microglial activation, which was attenuated in knockout mice or by zinc chelation.

    Conclusions:

    • Extracellular zinc acts as a direct trigger for microglial activation.
    • The activation pathway involves sequential signaling through NADPH oxidase, PARP-1, and NF-kappaB.
    • This mechanism highlights a novel role for zinc in neuroinflammation and its potential contribution to neurological disorders.