Cu/Zn-superoxide dismutase (GLY93→ALA) mutation alters AMPA receptor subunit expression and function and potentiates kainate-mediated toxicity in motor neurons in culture

Alida Spalloni, Federica Albo, Francesca Ferrari, Nicola Mercuri, Giorgio Bernardi, Cristina Zona, Patrizia Longone

Research output: Contribution to journalArticle

Abstract

The cause of the selective degeneration of motor neurons in amyotrophic lateral sclerosis (ALS) remains a mystery. One potential pathogenic mechanism is excitotoxicity due to disturbances of glutamatergic neurotransmission, particularly via AMPA-sensitive glutamate receptors. We report here that motor neurons from a familial ALS-linked superoxide dismutase (SOD1) mutant G93A mouse show an higher susceptibility to kainate-induced excitotoxicity. Moreover, they expressed GluR3 and GluR4 mRNA at detectable levels more frequently, with a modified electrophysiology when compared with control and wild-type SOD1 motor neurons. Thus, the SOD1 G93A mutation causes changes in the AMPA-receptor expression and function, as well as a susceptibility to kainate-mediated excitotoxicity, which may promote the motor neuron degeneration seen in ALS.

Original languageEnglish
Pages (from-to)340-350
Number of pages11
JournalNeurobiology of Disease
Volume15
Issue number2
DOIs
Publication statusPublished - Mar 2004

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Keywords

  • ALS
  • AMPAR
  • Amyotrophic lateral sclerosis
  • Excitotoxicity
  • G93A
  • Glutamate receptors
  • Motor neuron
  • Mutated (Gly93→Ala) form of SOD1
  • ScRT-PCR
  • Selective vulnerability
  • Superoxide dismutase-1

ASJC Scopus subject areas

  • Neurology

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