title: Self-regeneration of neuromuscular function following soman and VX poisoning in spinal cord-skeletal muscle cocultures.
abstract: Aside from nerve agents, various highly toxic pesticides belong to the group of organophosphorus (OP) compounds, thereby causing a large number of intoxications every year. Unfortunately, there are still shortcomings in the current treatment for OP poisoning and research on novel therapeutic options is restricted in several aspects. In this study we investigated the suitability of organotypic cocultures for pharmacological in vitro studies involving OP compounds. These slice cultures are derived from murine spinal cord and muscle tissue forming functional neuromuscular synapses, which trigger spontaneous contractions of muscle fibers. Using video microscopy to quantify muscle activity, we assessed the viability of cocultures after exposure to soman and VX, and the associated loss and recovery of neuromuscular function. Antidotal treatment was not provided. The application of nerve agents led to an almost complete loss of muscle activity. However, cell cultures regained equivalent muscular function to the control situation three and seven days after intoxication. In summary, the tested in vitro system could be a promising tool for the investigation of long term effects and therapeutic options for OP poisoning.
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany; Department of Anaesthesiology, Experimental Anaesthesiology Section, Eberhard-Karls-University, Waldhoernlestrasse 22, 72072 Tuebingen, Germany. Electronic address: isabel.weimer@uni-tuebingen.de.
authors.forename: Isabel
authors.initials: I
authors.lastname: Weimer
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Worek
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Seeger
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Thiermann
authors.affiliation: Department of Anaesthesiology, Experimental Anaesthesiology Section, Eberhard-Karls-University, Waldhoernlestrasse 22, 72072 Tuebingen, Germany.
authors.forename: Veit-Simon
authors.initials: VS
authors.lastname: Eckle
authors.affiliation: Department of Anaesthesiology, Experimental Anaesthesiology Section, Eberhard-Karls-University, Waldhoernlestrasse 22, 72072 Tuebingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Grasshoff
authors.affiliation: Department of Anaesthesiology, Experimental Anaesthesiology Section, Eberhard-Karls-University, Waldhoernlestrasse 22, 72072 Tuebingen, Germany; Werner-Reichardt-Centre for Integrative Neuroscience, Eberhard-Karls-University, 72076 Tuebingen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Antkowiak
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000633:toxicity*; D018920:Coculture Techniques; D008810:Mice, Inbred C57BL; D018715:Microscopy, Video; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D020127:Recovery of Function; D012038:Regeneration; D012999:Soman / Q000633:toxicity*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D046509:Tissue Culture Techniques
chemical_list: D002619:Chemical Warfare Agents; D009946:Organothiophosphorus Compounds; D012999:Soman; C009680:VX-agent
keywords: AChE inhibition; Neuromuscular junction; Organophosphorus compounds; Self-regeneration; Spinal cord—skeletal muscle cocultures