Comparative Transcriptome of Dorsal Root Ganglia Reveals Distinct Etiologies of Paclitaxel- and Oxaliplatin-induced Peripheral Neuropathy in Rats. (15th April 2023)

• Record Type: Journal Article
• Authors: Sun, Wuping; Hao, Yue; Li, Rongzhen; Ho, Idy Hiu Ting; Wu, Songbin; Li, Nan; Ba, Xiyuan; Wang, Jie; Xiong, Donglin; Jiang, Changyu; Xiao, Lizu; Liu, Xiaodong
• Is Part Of: Neuroscience. Volume 516(2023)
• Page Start: 1
• Page End: 14
• Publication Date: 2023-04-15
• Subjects: chemotherapy-induced peripheral neuropathy -- paclitaxel-induced peripheral neuropathy -- oxaliplatin-induced peripheral neuropathy -- mechanical allodynia -- thermal hyperalgesia -- RNAseq; Atf3 activating transcription factor 3 -- CIPN chemotherapy-induced peripheral neuropathy -- DEGs differentially expressed genes -- DRGs dorsal root ganglia -- GO gene ontology; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2023.02.007
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: 320 and 150 DEGs are identified after oxaliplatin and paclitaxel treatment. Only 17 DEGs are commonly dysregulated by two reagents. Paclitaxel treatment is associated with neuronal changes. Dividing cells and neuroinflammation are affected by oxaliplatin. 28 out of 29 biological processes occur in opposite modulations. Abstract: Chemotherapy-induced peripheral neuropathy is one of the most common side effects of anticancer therapy. It is anticipated that chemotherapies with different mechanisms of action may affect somatosensory neurons differently. This study aimed to explore similar and differential etiologies of oxaliplatin- and paclitaxel-induced neuropathy by comparing the transcriptomes of dorsal root ganglia (DRGs). We retrieved our previously published transcriptome data of DRGs extracted from vehicle-, oxaliplatin- and paclitaxel-treated rats (GSE160543), to analyze in parallel the differentially expressed genes (DEGs) and Gene ontology (GO) terms enrichment. We found that both oxaliplatin and paclitaxel treatments consistently produced mechanical allodynia, thermal hyperalgesia, and cold hyperalgesia in rats. Compared to vehicle, 320 and 150 DEGs were identified after oxaliplatin and paclitaxel treatment, respectively. Only 17 DEGs were commonly dysregulated by the two reagents. Activating transcription factor 3 (Atf3), a marker of nerve injury, was elevated only after paclitaxel treatment. GO analysis suggested that paclitaxel treatment was associated with neuronal changes characterized by numerous terms that are related to synaptic transmission, while oxaliplatin was more likely to affect dividing cells (e.g., the glia) and neuroinflammation. Notably, 29 biological processes GO terms were commonly enriched in response to both drugs. However, 28 out of 29 terms were oppositely modulated. This study suggests that distinct mechanisms underly paclitaxel- and oxaliplatin-induced neuropathy. Paclitaxel might directly affect somatosensory neurons while oxaliplatin primarily targets dividing cells and immune cells.