Single cell RNA-sequencing of male and female dorsal root ganglia (DRG) following Bortezomib (BTZ) or vehicle (VEH) administration.
Peripheral neuropathies are the most common neurodegenerative diseases affecting more than 20 million people in the USA alone. Chemotherapy, including treatment with the highly effective drug bortezomib (BTZ), is a frequent cause of peripheral neuropathy. We demonstrated recently that while some chemotherapeutics exert direct toxic effects on axons, BTZ leads to axon degeneration via signals from neuronal somata, which reside in the dorsal root ganglia (DRG). However, what these signals are and how they arise is unknown. To address this question, we treated mice intravenously with BTZ twice weekly for 8 weeks and determined the impact on DRG gene expression via single cell RNA-sequencing. Overall design: In these experiments we used wild-type mice (Balb/cJ mice own colony, average age 13 weeks) to test the effects of bortezomib treatment on peripheral neuropathy. Vehicle (5% 100% EtOH, 5% Tween-80, 90% Sterile Saline) or bortezomib (2 mg/ml in 100% ethanol) (Millipore Sigma) dissolved in 5% Tween-80, 90% Sterile Saline (0.1 mg/ml) was administered intravenously by tail vein injection twice weekly at a dose of 0.8 mg/kg for 8 weeks. Following administration, DRG tissues were isolated and analyzed using scRNAseq.