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Microglia as a Surrogate Biosensor to Determine Nanoparticle Neurotoxicity
08:37

Microglia as a Surrogate Biosensor to Determine Nanoparticle Neurotoxicity

Published on: October 25, 2016

Dopamine quinones activate microglia and induce a neurotoxic gene expression profile: relationship to

Donald M Kuhn1, Dina M Francescutti-Verbeem, David M Thomas

  • 1John D. Dingell VA Medical Center, Research & Development Service (11R), 4646 John R, Detroit, MI 48201, USA. donald.kuhn@wayne.edu

Annals of the New York Academy of Sciences
|November 16, 2006
PubMed

Insights

Methamphetamine neurotoxicity involves dopamine-quinone species activating microglia. This activation alters gene expression, potentially amplifying damage to dopamine nerve endings in the brain.

Area of Science:

  • Neuroscience
  • Toxicology
  • Neuroinflammation

Background:

  • Methamphetamine (METH) intoxication causes persistent damage to dopamine (DA) nerve endings.
  • Microglial activation is implicated in METH-induced neurotoxicity.
  • Dopamine (DA) plays a role in METH neurotoxicity, possibly via quinone formation.

Purpose of the Study:

  • To investigate the role of dopamine-quinones (DAQ) in microglial activation.
  • To analyze the impact of DAQ on microglial gene expression.

Main Methods:

  • Cultured microglial cells were treated with DAQ.
  • Microarray analysis was used to assess changes in microglial gene expression.

Main Results:

  • DAQ induced time-dependent activation of microglial cells.
  • 101 genes were significantly altered in expression by DAQ (73 increased, 28 decreased).
  • Upregulated genes included those related to inflammation; downregulated genes included those associated with neuronal protection.

Conclusions:

  • DAQ contributes to early microglial activation in METH intoxication.
  • DAQ alters the expression of a broad panel of genes in microglia.
  • This study links oxidative stress, DA conversion to DAQ, and microglial activation in a cascade amplifying METH neurotoxicity.

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