Finno, Carrie J. and Chen, Yingying and Park, Seojin and Lee, Jeong Han and Perez-Flores, Maria Cristina and Choi, Jinsil and Yamoah, Ebenezer N. (2022) Cisplatin Neurotoxicity Targets Specific Subpopulations and K+ Channels in Tyrosine-Hydroxylase Positive Dorsal Root Ganglia Neurons. Frontiers in Cellular Neuroscience, 16. ISSN 1662-5102
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Abstract
Among the features of cisplatin chemotherapy-induced peripheral neuropathy are chronic pain and innocuous mechanical hypersensitivity. The complete etiology of the latter remains unknown. Here, we show that cisplatin targets a heterogeneous population of tyrosine hydroxylase-positive (TH+) primary afferent dorsal root ganglion neurons (DRGNs) in mice, determined using single-cell transcriptome and electrophysiological analyses. TH+ DRGNs regulate innocuous mechanical sensation through C-low threshold mechanoreceptors. A differential assessment of wild-type and vitamin E deficient TH+ DRGNs revealed heterogeneity and specific functional phenotypes. The TH+ DRGNs comprise; fast-adapting eliciting one action potential (AP; 1-AP), moderately-adapting (≥2-APs), in responses to square-pulse current injection, and spontaneously active (SA). Cisplatin increased the input resistance and AP frequency but reduced the temporal coding feature of 1-AP and ≥2-APs neurons. By contrast, cisplatin has no measurable effect on the SA neurons. Vitamin E reduced the cisplatin-mediated increased excitability but did not improve the TH+ neuron temporal coding properties. Cisplatin mediates its effect by targeting outward K+ current, likely carried through K2P18.1 (Kcnk18), discovered through the differential transcriptome studies and heterologous expression. Studies show a potential new cellular target for chemotherapy-induced peripheral neuropathy and implicate the possible neuroprotective effects of vitamin E in cisplatin chemotherapy.
Item Type: | Article |
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Subjects: | Article Archives > Medical Science |
Depositing User: | Unnamed user with email support@articlearchives.org |
Date Deposited: | 05 Apr 2023 05:35 |
Last Modified: | 21 Oct 2024 04:12 |
URI: | http://archive.paparesearch.co.in/id/eprint/948 |