title: Mutant SOD1(G93A) microglia are more neurotoxic relative to wild-type microglia.
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.
authors.affiliation: 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.
authors.forename: Qin
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: 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.
authors.forename: Weihua
authors.initials: W
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: David R
authors.initials: DR
authors.lastname: Beers
authors.affiliation: 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.
authors.forename: Albert A
authors.initials: AA
authors.lastname: Yen
authors.affiliation: 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.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Xie
authors.affiliation: 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.
authors.forename: Jenny S
authors.initials: JS
authors.lastname: Henkel
authors.affiliation: 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.
authors.forename: Stanley H
authors.initials: SH
authors.lastname: Appel
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D002450:Cell Communication / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D002478:Cells, Cultured; D002490:Central Nervous System / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D018920:Coculture Techniques; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000201:enzymology*; D009046:Motor Neurons / Q000201:enzymology*; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009569:Nitric Oxide; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase