title: Complement upregulation and activation on motor neurons and neuromuscular junction in the SOD1 G93A mouse model of familial amyotrophic lateral sclerosis.
abstract: Complement activation products are elevated in cerebrospinal fluid, spinal cord and motor cortex of patients with amyotrophic lateral sclerosis (ALS) but are untested in models. We determined complement expression and activation in the SOD1 G93A mouse model of familial ALS (fALS). At 126days, C3 mRNA was upregulated in spinal cord and C3 protein accumulated in astrocytes and motor neurons. C3 activation products C3b/iC3b were localized exclusively on motor neurons. At the neuromuscular junction, deposits of C3b/iC3b and C1q were detected at day 47, before the appearance of clinical symptoms, and remained detectable at symptomatic stage (126days). Our findings implicate complement in the denervation of the muscle endplate by day 47 and destruction of the neuromuscular junction and spinal neuron loss by day 126 in the SOD1 G93A mouse model of fALS.
authors.affiliation: Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff, UK.
authors.forename: Bianca
authors.initials: B
authors.lastname: Heurich
authors.forename: Nawal Bahia
authors.initials: NB
authors.lastname: El Idrissi
authors.forename: Rossen M
authors.initials: RM
authors.lastname: Donev
authors.forename: Susanne
authors.initials: S
authors.lastname: Petri
authors.forename: Peter
authors.initials: P
authors.lastname: Claus
authors.forename: James
authors.initials: J
authors.lastname: Neal
authors.forename: B Paul
authors.initials: BP
authors.lastname: Morgan
authors.forename: Valeria
authors.initials: V
authors.lastname: Ramaglia
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D003176:Complement C3 / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000276:immunology* / Q000378:metabolism; D009469:Neuromuscular Junction / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D003176:Complement C3; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase