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

Abstract

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 nontraditional 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.

Cellular Pathogenesis of Chemotherapy-Induced Peripheral Neuropathy: Insights From Drosophila and Human-Engineered Skin Models

“…The study then ranked the models in their efficacy in representing CIPN, as evaluated by assessing mechanical allodynia, thermal hyper and hypoalgesia, histological damage to the peripheral nervous system, and functional neurophysiological changes (73). The most efficacious models were determined to be rats and mice; however, the study also recognized that more research is needed in other potentially effective models, including Drosophila and zebrafish, which showed a consistent efficacy in driving CIPN phenotypes using paclitaxel, cisplatin, and bortezomib (65,73,75).…”

“…Non-mammalian in vivo models, Drosophila, zebrafish, and C. elegans provide advantages in genetics and live monitoring of neuron phenotypes and the surrounding environment (75). While sensory neurons in non-mammalian models have several differences from mammalian counterparts, these models are advantageous and complementary to mammalian models.…”

Therapeutic Potential of CKD-504, a Novel Selective Histone Deacetylase 6 Inhibitor, in a Zebrafish Model of Neuromuscular Junction Disorders

“…In this study, we investigated the efficacy of HDAC6 inhibition in repairing NMJ defects in peripheral neuropathies. We first generated an NMJ disease model using zebrafish ( Danio rerio ), which is generally used for drug screening, as well as for modeling peripheral neuropathies such as CMT ( Cirrincione and Rieger, 2020 ; Ennerfelt et al, 2019 ; Ponomareva et al, 2016 ). We investigated the effects of several HDAC6 inhibitors on recovery from NMJ defects, including muscle dysfunction.…”

Bimodal Imaging of Mouse Peripheral Nerves with Chlorin Tracers

“…In response to this shortfall, researchers have sought to identify distinct molecular and cellular changes associated with specific pain pathologies, but this research is still challenging. 7,8 Even though a number of studies have investigated targets and methods to enhance visualization of the peripheral nervous system, 9−12 relatively few cases have successfully achieved this goal by means of attaining high specific uptake or high targetto-background ratios. In 2011, the groups of Frangioni and Nguyen reported the use of fluorescently tagged nerve tracers, namely, GE3082 and FAM-NP41, for the visualization of sciatic nerves.…”

“…The early identification of nerves affected by chemotherapy could provide tremendous benefits, including the potential to stratify individuals early, before severe neuropathy develops. In response to this shortfall, researchers have sought to identify distinct molecular and cellular changes associated with specific pain pathologies, but this research is still challenging. , …”