Mit e. Medpedia Podcast. Apps Newsletter Abo-Shop. Springer Medizin. Suche Suchbegriffe eingeben Suchen. Archives of Toxicology. Abstract Poisoning with the organophosphorus nerve agent VX can be life-threatening due to limitations of the standard therapy with atropine and oximes.
To date, the underlying pathomechanism of VX affecting the neuromuscular junction has not been fully elucidated structurally. Results of recent studies investigating the effects of VX were obtained from cells of animal origin or immortalized cell lines limiting their translation to humans. To overcome this limitation, motor neurons MN of this study were differentiated from in-house feeder- and integration-free-derived human-induced pluripotent stem cells hiPSC by application of standardized and antibiotic-free differentiation media with the aim to mimic human embryogenesis as closely as possible.
For the first time, VX was shown to trigger neuronal cell death and decline in neurite outgrowth in hiPSC-derived MN in a time- and concentration-dependent manner involving the activation of the intrinsic as well as the extrinsic pathway of apoptosis.
Consistent with this, MN morphology and neurite network were altered time and concentration-dependently. Thus, MN represent a valuable tool for further investigation of the pathomechanism after VX exposure. These findings might set the course for the development of a promising human neuromuscular test model and patient-specific therapies in the future. Simone Rothmiller and Annette Schmidt have contributed equally to this work.
Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Introduction The highly toxic chemical warfare nerve agent VX is structurally related to widely used pesticides and belongs to the group of organophosphorus compounds OPC Wang et al. Although the development, production, stockpiling, and use of chemical warfare agents has been banned by the Chemical Weapons Convention since and is supervised by the Organisation for Prohibition of Chemical Weapons OPCW , the threat still remains as recent deployments in Syria and assassinations in Japan or Malaysia demonstrate Organisation for the Prohibition of Chemical Weapons ; Nakagawa and Tu ; Tu ; John et al.
