PUBLICATION
Schwann cell transient receptor potential ankyrin 1 (TRPA1) ortholog in zebrafish larvae mediates chemotherapy-induced peripheral neuropathy
- Authors
- Bellantoni, E., Marini, M., Chieca, M., Gabellini, C., Crapanzano, E.L., Souza Monteiro de Araujo, D., Nosi, D., Roschi, L., Landini, L., De Siena, G., Pensieri, P., Mastricci, A., Scuffi, I., Geppetti, P., Nassini, R., De Logu, F.
- ID
- ZDB-PUB-240906-12
- Date
- 2024
- Source
- British journal of pharmacology 181(23): 4859-4873 (Journal)
- Registered Authors
- Keywords
- Schwann cells, nociceptive behaviours, oxaliplatin, oxidative stress, transient receptor potential ankyrin 1 (TRPA1)
- MeSH Terms
-
- Animals
- TRPA1 Cation Channel*/genetics
- TRPA1 Cation Channel*/metabolism
- Zebrafish*
- Humans
- Schwann Cells*/drug effects
- Schwann Cells*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Antineoplastic Agents/pharmacology
- Antineoplastic Agents/toxicity
- Reactive Oxygen Species/metabolism
- Mice
- Larva*
- Oxaliplatin*/toxicity
- Peripheral Nervous System Diseases/chemically induced
- Peripheral Nervous System Diseases/metabolism
- Mice, Inbred C57BL
- HEK293 Cells
- Male
- PubMed
- 39238161 Full text @ Br. J. Pharmacol.
Citation
Bellantoni, E., Marini, M., Chieca, M., Gabellini, C., Crapanzano, E.L., Souza Monteiro de Araujo, D., Nosi, D., Roschi, L., Landini, L., De Siena, G., Pensieri, P., Mastricci, A., Scuffi, I., Geppetti, P., Nassini, R., De Logu, F. (2024) Schwann cell transient receptor potential ankyrin 1 (TRPA1) ortholog in zebrafish larvae mediates chemotherapy-induced peripheral neuropathy. British journal of pharmacology. 181(23):4859-4873.
Abstract
Background and purpose The oxidant sensor transient receptor potential ankyrin 1 (TRPA1) channel expressed by Schwann cells (SCs) has recently been implicated in several models of neuropathic pain in rodents. Here we investigate whether the pro-algesic function of Schwann cell TRPA1 is not limited to mammals by exploring the role of TRPA1 in a model of chemotherapy-induced peripheral neuropathy (CIPN) in zebrafish larvae.
Experimental approach We used zebrafish larvae and a mouse model to test oxaliplatin-evoked nociceptive behaviours. We also performed a TRPA1 selective silencing in Schwann cells both in zebrafish larvae and mice to study their contribution in oxaliplatin-induced CIPN model.
Key results We found that zebrafish larvae and zebrafish TRPA1 (zTRPA1)-transfected HEK293T cells respond to reactive oxygen species (ROS) with nociceptive behaviours and intracellular calcium increases, respectively. TRPA1 was found to be co-expressed with the Schwann cell marker, SOX10, in zebrafish larvae. Oxaliplatin caused nociceptive behaviours in zebrafish larvae that were attenuated by a TRPA1 antagonist and a ROS scavenger. Oxaliplatin failed to produce mechanical allodynia in mice with Schwann cell TRPA1 selective silencing (Plp1+-Trpa1 mice). Comparable results were observed in zebrafish larvae where TRPA1 selective silencing in Schwann cells, using the specific Schwann cell promoter myelin basic protein (MBP), attenuated oxaliplatin-evoked nociceptive behaviours.
Conclusion and implications These results indicate that the contribution of the oxidative stress/Schwann cell/TRPA1 pro-allodynic pathway to neuropathic pain models seems to be conserved across the animal kingdom.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping