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The role of monoamine metabolism in oxidative glutamate toxicity

P Maher1, J B Davis

  • 1Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|October 15, 1996
PubMed

Insights

Glutamate-induced neuronal cell death, particularly via the oxidative pathway, relies on free radicals from monoamine metabolism. Inhibiting monoamine uptake or using specific MAO-A inhibitors blocks this toxicity, suggesting a novel enzyme involvement.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Glutamate excitotoxicity is a significant factor in neuronal cell death.
  • This toxicity occurs via receptor-mediated or oxidative pathways, both linked to free radical production.
  • Antioxidants mitigate cell death, confirming the role of free radicals.

Purpose of the Study:

  • To investigate the role of monoamine metabolism in glutamate-induced neuronal cell death via the oxidative pathway.
  • To identify the specific enzymes and mechanisms involved in generating free radicals during glutamate toxicity.

Main Methods:

  • Utilized a neuronal cell line to study glutamate toxicity.
  • Administered glutamate and observed cell death.
  • Tested the effects of monoamine oxidase (MAO) inhibitors (type-A and type-B) and monoamine uptake inhibitors.
  • Assessed the role of monoamine metabolism in free radical production.

Main Results:

  • Glutamate toxicity via the oxidative pathway was dependent on monoamine metabolism as a source of free radicals.
  • MAO type-A inhibitors showed toxicity inhibition only at high concentrations, not typical for classical MAO-A inhibition.
  • MAO type-B inhibitors did not inhibit toxicity at any concentration.
  • Agents blocking monoamine uptake effectively inhibited glutamate toxicity.

Conclusions:

  • A distinct enzyme, separate from MAO, appears to be involved in the monoamine metabolism contributing to glutamate toxicity.
  • A direct link exists between glutamate excitotoxicity and monoamine metabolism.
  • Findings have implications for understanding and treating neurodegenerative diseases involving glutamate toxicity.

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