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Abstract：
This study investigated the time course of gene expression changes during the progression of persistent painful neuropathy caused by paclitaxel (PTX) in male and female mouse hindpaws and dorsal root ganglia (DRG). Bulk RNA-seq was used to examine these gene expression changes at 1, 16, and 31 days post-last PTX. At these time points, differentially expressed genes (DEGs) were predominantly related to the reduction or increase in epithelial, skin, bone, and muscle development and to angiogenesis, myelination, axonogenesis, and neurogenesis. These processes are accompanied by the regulation of DEGs related to the cytoskeleton, extracellular matrix organization, and cellular energy production. This gene plasticity during the progression of persistent painful neuropathy could be interpreted as a biological process linked to tissue regeneration/degeneration. In contrast, gene plasticity related to immune processes was minimal at 1-31 days after PTX. It was also noted that despite similarities in biological processes and pain chronicity between males and females, specific DEGs differed dramatically according to sex. The main conclusions of this study are that gene expression plasticity in hindpaw and DRG during PTX neuropathy progression similar to tissue regeneration and degeneration, minimally affects immune system processes and is heavily sex-dependent at the individual gene level.
摘要：
这项研究调查了雄性和雌性小鼠后爪和背根神经节（DRG）中紫杉醇（PTX）引起的持续性疼痛性神经病进展过程中基因表达变化的时间过程。在最后一个PTX后1、16和31天，使用BulkRNA-seq检查这些基因表达变化。在这些时间点,差异表达基因（DEGs）主要与上皮的减少或增加有关，皮肤,骨头,肌肉发育和血管生成，髓鞘形成,轴突发生，和神经发生。这些过程伴随着与细胞骨架相关的DEGs的调节，细胞外基质组织，和细胞能量生产。在持续性疼痛性神经病的进展过程中，这种基因可塑性可以解释为与组织再生/变性有关的生物学过程。相比之下,与免疫过程相关的基因可塑性在PTX后1-31天最小。还指出，尽管男性和女性在生物学过程和疼痛慢性方面有相似之处，具体的DEGs根据性别有很大差异。本研究的主要结论是，PTX神经病变进展过程中后爪和DRG的基因表达可塑性与组织再生和变性相似，对免疫系统过程的影响最小，并且在个体基因水平上严重依赖性别。
