Characterisation of a Cell Culture System for Investigating Nerve Agent Neurotoxicology. Part 1

Abstract : Neuroblastoma cell lines NB41A3 and SH-SY5Y were evaluated as an in vitro model system for studying organophosphorus (OP) chemical toxicity in central nervous system (CNS) cell lineages. Optimal culturing conditions, neuronal differentiation protocols and appropriate cholinergic gene expression were confirmed. The presence of muscarinic receptors and acetylcholinesterase activity was determined. Importantly, differential acetylcholinesterase inhibition by OP chemicals was demonstrated in live cells. This work has developed expertise in neuronal cell culture, confocal microscopy and enzyme activity assays that will provide the basis for an ongoing research programme. The neuroblastoma cell lines chosen can potentially be used as a model for investigating the toxicity of a range of CNS-acting chemicals of interest to the Department of Defence.