Cognitive impairment resulting from treatment with docetaxel, doxorubicin, and cyclophosphamide.
Cognitive impairment resulting from treatment with docetaxel, doxorubicin, and cyclophosphamide.
复制标题
多西紫杉醇、阿霉素和环磷酰胺治疗引起的认知损害。
DOI：
10.1016/j.brainres.2021.147397
复制
发表时间：
2021-06-01
期刊：
影响因子：
2.9
通讯作者：
中科院分区：
文献类型：
--
作者：
乳腺癌是女性中最常见的癌症，据估计，约30%的女性新诊断的癌症是乳腺癌。虽然治疗乳腺癌的进展已使平均5年生存率达到90%，但许多幸存者因化疗治疗而出现认知障碍。阿霉素、环磷酰胺和多西他赛（TAC）通常作为乳腺癌治疗药物使用;然而，很少有研究测试TAC的认知影响。在本研究中，12周龄雌性C57 BL/6小鼠接受4周一次的盐水或多柔比星和环磷酰胺联合治疗的腹膜内注射，随后接受4周一次的多西他赛注射。在最后一次注射后四周，在Y-迷宫和Morris水迷宫中测试小鼠的视皮层依赖性认知表现。在Y-迷宫测试期间，暴露于TAC的小鼠表现出损伤。在水迷宫评估期间，所有动物都能够定位可见和隐藏的平台位置。然而，接受TAC的小鼠在探测试验日表现出空间记忆保持的显著损伤。TAC处理显著降低海马齿状回区域树枝状化的树突复杂性。此外，比较蛋白质组学分析揭示了与认知功能障碍相关的关键代谢和信号传导途径中的蛋白质下调，如氧化磷酸化、肝配蛋白信号传导和钙信号传导。
Breast cancer is the most commonly diagnosed cancer among women and it is estimated that about 30% of newly diagnosed cancers in women will be breast cancers. While advancements in treating breast cancer have led to an average 5-year survival rate of 90%, many survivors experience cognitive impairments as a result of chemotherapy treatment. Doxorubicin, cyclophosphamide, and docetaxel (TAC) are commonly administered as breast cancer treatments; however, there are few studies that have tested the cognitive effects of TAC. In the current study, 12-week-old female C57BL/6 mice received 4 weekly intraperitoneal injections of either saline or a combination therapy of doxorubicin and cyclophosphamide followed by 4 weekly docetaxel injections. Four weeks after the last injection, mice were tested for hippocampus-dependent cognitive performance in the Y-maze and the Morris water maze. During Y-maze testing, mice exposed to TAC exhibited impairment. During the water maze assessment, all animals were able to locate the visible and hidden platform locations. However, mice that received the TAC presented with a significant impairment in spatial memory retention on the probe trial days. TAC treatment significantly decreases the dendritic complexity of arborization in the dentate gyrus region of the hippocampus. In addition, comparative proteomic analysis revealed downregulation of proteins within key metabolic and signaling pathways associated with cognitive dysfunction, such as oxidative phosphorylation, ephrin signaling, and calcium signaling.
登录
查看更多内容
影响因子：
2.7
作者：
Callaghan, Charlotte K.;O'Mara, Shane M.
通讯作者：
O'Mara, Shane M.
表达人类野生型Tau的转基因小鼠的树突复杂性和脊柱形态的变化。
影响因子：
3.1
作者：
Dickstein, Dara L.;Brautigam, Hannah;Stockton, Steven D., Jr.;Schmeidler, James;Hof, Patrick R.
通讯作者：
Hof, Patrick R.
影响因子：
158.5
作者：
Joensuu, H;Kellokumpu-Lehtinen, P;Isola, J
通讯作者：
Isola, J
影响因子：
2.4
作者：
Janelsins, Michelle C.;Roscoe, Joseph A.;Gross, Robert A.
通讯作者：
Gross, Robert A.
影响因子：
4.3
作者：
Ellenbroek B;Youn J
通讯作者：
Youn J