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Mutant SOD1(G93A) microglia are more neurotoxic relative to wild-type microglia.

Authors
  • Xiao, Qin1
  • Zhao, Weihua1
  • Beers, David R1
  • Yen, Albert A1
  • Xie, Wenjie1
  • Henkel, Jenny S1
  • Appel, Stanley H1
  • 1 Department of Neurology, Methodist Neurological Institute, Houston, Texas, USADepartment of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, ChinaDepartment of Neurology, Baylor College of Medicine, Houston, Texas, USA. , (China)
Type
Published Article
Journal
Journal of neurochemistry
Publication Date
Sep 01, 2007
Volume
102
Issue
6
Pages
2008–2019
Identifiers
DOI: 10.1111/j.1471-4159.2007.04677.x
PMID: 17555556
Source
Medline
License
Unknown

Abstract

Recent studies suggest that microglia over-expressing mutant human superoxide dismutase (mSOD1(G93A)) 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, mSOD1(G93A) microglia released more nitric oxide, more superoxide, and less insulin-like growth factor-1 than wild-type microglia. In microglia/motoneuron co-cultures, mSOD1(G93A) microglia induced more motoneuron death and decreased neurite numbers and length compared with wild-type microglia. Mutant SOD1(G93A) 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 mSOD1(G93A) co-cultures, suggesting the important role of nitric oxide in microglia-induced motoneuron injury. Thus, relative to wild-type microglia, mSOD1(G93A) microglia were more neurotoxic and induced more motoneuron injury than similarly treated wild-type microglia.

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