Detection method of the adjacent motor neuronal death in an in vitro co-culture model of familial ALS-associated Cu/Zn superoxide dismutase.
Mutations in Cu/Zn-superoxide dismutase (SOD1) gene have been identified in familial amyotrophic lateral sclerosis. Motor neuron degeneration subsequently spreads to contiguous neurons of the motor systems. We developed an in vitro disease model with motor neuron-neuroblastoma hybrid cells (VSC4.1) constitutively expressing a mutant (G93A) SOD1. The extracellular effect upon adjacent motor neurons was determined using the substratum culture insert. The viability of VSC 4.1 was lowered by 26% in a co-culture of VSC 4.1 and G93A, which was reversed by Trolox, an antioxidant. This in vitro disease model confirmed the extracellular toxicity of the mutant SOD1 cells on the adjacent neurons by generating oxidative stress.
Park
Kyung-Seok
KS
Department of Neurology, Seoul Paik Hospital, Inje University, Seoul, Korea.
Kim
Hyun-Jung
HJ
Choi
Won-Jun
WJ
Kim
Manho
M
Lee
Kwang-Woo
KW
D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology* / Q000503:physiopathology*; D017209:Apoptosis / Q000502:physiology; D024201:Bystander Effect; D002452:Cell Count / Q000379:methods*; D002460:Cell Line; D002470:Cell Survival; D018920:Coculture Techniques / Q000379:methods; D006801:Humans; D009046:Motor Neurons / Q000473:pathology* / Q000502:physiology*; D009154:Mutation; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1