Analyzing chemotherapy-induced peripheral neuropathy in vivo using non-mammalian animal models

• Published in: Experimental neurology 2020-01, Vol.323, p.113090-113090, Article 113090
• Main Authors: Cirrincione, Anthony M., Rieger, Sandra
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - toxicity; Axon degeneration; Caenorhabditis elegans; Chemotherapy-induced peripheral neuropathy; CIPN; Disease Models, Animal; Drosophila; Drosophila melanogaster; in vivo imaging; Neurotoxicity Syndromes; Non-mammalian; Peripheral Nervous System Diseases - chemically induced; Review; Zebrafish; Zebrafish C. elegans
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2019.113090

Non-mammalian models of CIPN remain relatively sparse, but the knowledge gained from the few published studies suggest that these species have great potential to serve as a discovery platform for new pathways and underlying genetic mechanisms of CIPN. These models permit large-scale genetic and pharmacological screening, and they are highly suitable for in vivo imaging. CIPN phenotypes described in rodents have been confirmed in those models, and conversely, genetic players leading to axon de- and regeneration under conditions of chemotherapy treatment identified in these non-mammalian species have been validated in rodents. Given the need for non-traditional approaches with which to identify new CIPN mechanisms, these models bear a strong potential due to the conservation of basic mechanisms by which chemotherapeutic agents induce neurotoxicity. •C. elegans, Drosophila and zebrafish as chemotherapy-induced neurotoxicity models•In vivo imaging revealed new CIPN mechanisms with conserved functions in mammals.•NMNAT, DLK, and MORN are major players in the control of paclitaxel-induced axon degeneration.•ROS and altered microtubule function are aberrant in paclitaxel-induced peripheral neuropathy.•Epidermal damage contributes to paclitaxel neurotoxicity through activation of MMP-13.