Mutant SOD1G93A microglia are more neurotoxic relative to wild-type microglia

Qin Xiao, Weihua Zhao, David Beers, Albert A. Yen, Wenjie Xie, Jenny S. Henkel, Stanley H. Appel

Research output: Contribution to journalArticle

113 Scopus citations

Abstract

Recent studies suggest that microglia over-expressing mutant human superoxide dismutase (mSOD1G93A) may contribute to motoneuron death in a transgenic mouse model of familial amyotrophic lateral sclerosis. To further assess the relative neurotoxicity of wild-type microglia, mSOD1 G93A microglia, and microglia over-expressing wild-type human SOD1, we used primary cultures of microglia and motoneurons in the presence and absence of lipopolysaccharide stimulation. Following activation with lipopolysaccharide, mSOD1G93A microglia released more nitric oxide, more superoxide, and less insulin-like growth factor-1 than wild-type microglia. In microglia/motoneuron co-cultures, mSOD1G93A microglia induced more motoneuron death and decreased neurite numbers and length compared with wild-type microglia. Mutant SOD1G93A microglia also induced more motoneuron injury than microglia over-expressing wild-type human SOD1 in microglia/motoneuron co-cultures. Motoneuron survival was inversely correlated with nitrate + nitrite concentrations in mSOD1G93A co-cultures, suggesting the important role of nitric oxide in microglia-induced motoneuron injury. Thus, relative to wild-type microglia, mSOD1G93A microglia were more neurotoxic and induced more motoneuron injury than similarly treated wild-type microglia.

Original languageEnglish (US)
Pages (from-to)2008-2019
Number of pages12
JournalJournal of Neurochemistry
Volume102
Issue number6
DOIs
StatePublished - Sep 2007

Keywords

  • Amyotrophic lateral sclerosis
  • Insulin-like growth factor-1
  • Microglia
  • Motoneuron
  • Nitric oxide
  • Superoxide

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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