Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Beijing, PR China.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Beijing, PR China.
Neuroscience. 2020 Feb 1;426:168-178. doi: 10.1016/j.neuroscience.2019.11.031. Epub 2019 Dec 14.
Paclitaxel (PTX) is one of the most commonly used chemotherapeutic agents for various cancer diseases. Despite its advantages, PTX also causes behavioral deficits related to nervous-system dysfunction, such as neuropathic pain, depression, anxiety, and cognitive impairments. The prefrontal cortex (PFC) is one of the areas that is susceptible to adverse effects of chemotherapeutic agents. Therefore, the present study was designed to examine sex-biased behavioral deficits and whole-transcriptome changes in gene expression in the PFC of mice treated with vehicle or PTX. In this study, PTX (4 mg/kg) was injected intraperitoneally four times in mice every other day. Three weeks later, both PTX-treated male and female mice developed mechanical pain hypersensitivities, as indicated by increased paw withdrawal responses to 0.16-g von Frey filaments. Additionally, PTX-treated mice exhibited depression-like symptoms, as they exhibited increased immobility times in the forced swim test. PTX also induced cognitive impairment, as demonstrated via results of a novel object recognition (NOR) test and anxiety-like behavior in an elevated plus-maze test in male mice, but not in female mice. RNA sequencing and in-depth gene expression analysis of the PFC in paired vehicle and PTX-treated mice showed that PTX induced 1755 differentially expressed genes in the PFCs of male and female mice. Quantitative real-time RT-PCR verified that some gene expressions in the medial PFC (mPFC) were related to neurotransmission. In conclusion, this study identified a sex-biased effect of PTX on PFC function and gene expression, which provides a foundation for future studies to explore the precise mechanisms of PTX-induced behavioral deficits.
紫杉醇（PTX）是用于各种癌症疾病的最常用化疗药物之一。尽管它有优势，但 PTX 也会导致与神经系统功能障碍相关的行为缺陷，如神经病理性疼痛、抑郁、焦虑和认知障碍。前额叶皮层（PFC）是易受化疗药物不良影响的区域之一。因此，本研究旨在研究用载体或 PTX 处理的小鼠 PFC 中的性别偏倚行为缺陷和全转录组基因表达变化。在这项研究中，PTX（4mg/kg）每隔一天通过腹膜内注射四次注射到小鼠中。三周后，PTX 处理的雄性和雌性小鼠都出现了机械性疼痛过敏，表现为对 0.16g von Frey 纤维的爪撤回反应增加。此外，PTX 处理的小鼠表现出抑郁样症状，因为它们在强迫游泳试验中表现出更多的不动时间。PTX 还诱导认知障碍，如雄性小鼠新物体识别（NOR）测试和高架十字迷宫测试中的焦虑样行为所示，但在雌性小鼠中没有。配对的载体和 PTX 处理的小鼠的 PFC 的 RNA 测序和深入基因表达分析显示，PTX 在雄性和雌性小鼠的 PFC 中诱导了 1755 个差异表达基因。定量实时 RT-PCR 验证了内侧前额叶皮层（mPFC）中的一些基因表达与神经递质有关。总之，这项研究确定了 PTX 对 PFC 功能和基因表达的性别偏倚效应，为未来研究探索 PTX 诱导的行为缺陷的确切机制提供了基础。
