Demos-Davies Kimberly, Lawrence Jessica, Ferreira Clara, Seelig Davis
Department of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, Saint Paul, MN 55108, USA.
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Brain Sci. 2023 Dec 24;14(1):22. doi: 10.3390/brainsci14010022.
Cancer survivors experience cancer-related cognitive impairment (CRCI) secondary to treatment. Chemotherapy and radiation therapy independently contribute to cognitive dysfunction; however, the underlying mechanisms leading to dysfunction remain unclear. We characterized brain gene expression changes in a mouse model of CRCI to identify the mechanistic underpinnings. Eleven-to-twelve-week-old SKH1 mice were treated with doxorubicin (DOX), hindlimb radiation (RT), concurrent hindlimb radiation and doxorubicin (DOX-RT), or no treatment (control). Sixteen days following treatment, gene expression was measured from murine brains using the NanoString nCounter glial profiling panel. Gene expression was normalized and compared between groups. No two groups shared the same expression pattern, and only and were upregulated in multiple treatment groups. Brains from DOX-treated mice had upregulated , , , , and and downregulated expression compared to control brains. Brains from RT-treated mice demonstrated increased and and decreased and expression compared to control brains. Brains from DOX-RT-treated mice had upregulated , , , , , and expression and downregulated and expression compared to control brains. The gene expression changes demonstrated here highlight roles for neuronal transmission and oxidative stress in the pathogenesis of doxorubicin-related CRCI and inflammation in RT-related CRCI.
癌症幸存者会因治疗而出现癌症相关认知障碍（CRCI）。化疗和放疗各自都会导致认知功能障碍；然而，导致功能障碍的潜在机制仍不清楚。我们对CRCI小鼠模型中的脑基因表达变化进行了表征，以确定其机制基础。将11至12周龄的SKH1小鼠用阿霉素（DOX）、后肢放疗（RT）、后肢放疗与阿霉素联合治疗（DOX-RT）或不治疗（对照）。治疗后16天，使用NanoString nCounter神经胶质细胞分析面板测量小鼠大脑的基因表达。对基因表达进行标准化并在组间进行比较。没有两组具有相同的表达模式，并且只有 和 在多个治疗组中上调。与对照大脑相比，DOX治疗小鼠的大脑中 、 、 、 和 上调， 表达下调。与对照大脑相比，RT治疗小鼠的大脑中 和 增加， 和 表达减少。与对照大脑相比，DOX-RT治疗小鼠的大脑中 、 、 、 、 和 表达上调， 和 表达下调。此处显示的基因表达变化突出了神经元传递和氧化应激在阿霉素相关CRCI发病机制中的作用以及炎症在RT相关CRCI中的作用。
