ALS-linked Cu/Zn-SOD mutation impairs cerebral synaptic glucose and glutamate transport and exacerbates ischemic brain injury

Zhihong Guo, Mark S. Kindy, Inna Kruman, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

Although degeneration of lower motor neurons is the most striking abnormality in amyotrophic lateral sclerosis (ALS), more subtle alterations may occur in the brain. Mutations in copper/zinc superoxide dismutase (Cu/Zn- SOD) are responsible for some cases of inherited ALS, and expression of mutant Cu/Zn-SOD in transgenic mice results in progressive motor neuron loss and a clinical phenotype similar to that of ALS patients. It is now reported that Cu/Zn-SOD mutant mice exhibit increased vulnerability to focal ischemic brain injury after transient occlusion of the middle cerebral artery. Levels of glucose and glutamate transport in cerebral cortex synaptic terminals were markedly decreased and levels of membrane lipid peroxidation were increased in Cu/Zn-SQD mutant mice compared to nontransgenic mice. These findings demonstrate that mutant Cu/Zn-SOD may endanger brain neurons by a mechanism involving impairment of glucose and glutamate transporters. Moreover, our data demonstrate a direct adverse effect of the mutant enzyme on synaptic function.

Original languageEnglish (US)
Pages (from-to)463-468
Number of pages6
JournalJournal of Cerebral Blood Flow and Metabolism
Volume20
Issue number3
StatePublished - 2000
Externally publishedYes

Keywords

  • Amyotrophic lateral sclerosis
  • Excitotoxicity
  • Focal ischemia
  • Lipid peroxidation
  • Transgenic

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

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