Disruption of glial glutamate transport by reactive oxygen species produced in motor neurons

Shyam Rao, Hong Z. Yin, John H. Weiss

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Observations of elevated CSF glutamate in amyotrophic lateral sclerosis (ALS), together with findings that motor neurons are selectively vulnerable to glutamate receptor-mediated ("excitotoxic") injury, support an excitotoxic contribution to the motor neuron loss in the disease. However, the basis of the apparent loss of astrocytic glutamate transport capacity in affected areas of motor cortex and spinal cord, which probably underlies the extracellular glutamate elevations, is unexplained. Here, we find that glutamate induces far greater reactive oxygen species (ROS) generation in cultured motor neurons than in other spinal neurons. In addition, we found that the ROS seem to be able to leave the motor neurons and induce oxidation and disruption of glutamate uptake in neighboring astrocytes. Correspondingly, in a transgenic mouse model of ALS, protein oxidation was increased in regions immediately surrounding motor neurons. These results provide a mechanism that can account for the localized loss of glial glutamate transport seen in the disease. Furthermore, the observations lend support for a feedforward model involving reciprocal interactions between motor neurons and glia, which may prove useful in understanding ALS pathogenesis.

Original languageEnglish (US)
Pages (from-to)2627-2633
Number of pages7
JournalJournal of Neuroscience
Volume23
Issue number7
StatePublished - Apr 1 2003

Fingerprint

Motor Neurons
Neuroglia
Glutamic Acid
Reactive Oxygen Species
Amyotrophic Lateral Sclerosis
Glutamate Receptors
Motor Cortex
Astrocytes
Transgenic Mice
Spinal Cord
Neurons
Wounds and Injuries
Proteins

Keywords

  • AMPA
  • Amyotrophic lateral sclerosis
  • Cell culture
  • Excitotoxicity
  • Free radicals
  • Glutamate
  • Glutamate transport
  • Motor neuron
  • Nitrotyrosine
  • ROS
  • SOD

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Disruption of glial glutamate transport by reactive oxygen species produced in motor neurons. / Rao, Shyam; Yin, Hong Z.; Weiss, John H.

In: Journal of Neuroscience, Vol. 23, No. 7, 01.04.2003, p. 2627-2633.

Research output: Contribution to journalArticle

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