The Distant Molecular Effects on the Brain by Cancer Treatment.
The Distant Molecular Effects on the Brain by Cancer Treatment.
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DOI：
10.3390/brainsci14010022
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发表时间：
2023-12-24
期刊：
影响因子：
3.3
通讯作者：
中科院分区：
文献类型：
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作者：
癌症幸存者经历继发于治疗的癌症相关认知障碍（CRCI）。化疗和放疗独立地导致认知功能障碍;然而，导致功能障碍的潜在机制仍不清楚。我们描述了CRCI小鼠模型中大脑基因表达的变化，以确定其机制基础。用多柔比星（DOX）、后肢放射（RT）、后肢放射和多柔比星同时进行（DOX-RT）或不处理（对照）处理11至12周龄SKH 1小鼠。处理后16天，使用NanoString nCounter®胶质细胞谱分析板测量小鼠脑的基因表达。将基因表达标准化并在组间进行比较。没有两个组共享相同的表达模式，只有Gnb 1和Srpr在多个治疗组中上调。与对照组相比，DOX处理小鼠的大脑上调了Atf 2、Atp 5 b、Gnb 1、Rad 23 b和Srpr，下调了Sirt 5的表达。与对照组相比，RT处理小鼠的大脑表现出Abcg 2和Fgf 2表达增加，C1 qa和C1 qb表达减少。与对照组相比，DOX-RT处理小鼠的脑上调了阿达尔、E2 f3、Erlec 1、Gnb 1、Srpr、Vim和Pdgfra表达，下调了Rock 2和Inpp 5 f表达。基因表达的变化表明，在阿霉素相关的CRCI和RT相关的CRCI炎症的发病机制中，神经元传递和氧化应激的作用。
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 Gnb1 and Srpr were upregulated in multiple treatment groups. Brains from DOX-treated mice had upregulated Atf2, Atp5b, Gnb1, Rad23b, and Srpr and downregulated Sirt5 expression compared to control brains. Brains from RT-treated mice demonstrated increased Abcg2 and Fgf2 and decreased C1qa and C1qb expression compared to control brains. Brains from DOX-RT-treated mice had upregulated Adar, E2f3, Erlec1, Gnb1, Srpr, Vim, and Pdgfra expression and downregulated Rock2 and Inpp5f 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.
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影响因子：
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影响因子：
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3.2
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