Piperlongumine as a Neuro-Protectant in Chemotherapy Induced Cognitive Impairment.
Piperlongumine as a Neuro-Protectant in Chemotherapy Induced Cognitive Impairment.
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曲马多明作为化疗所致认知障碍的神经保护剂。
DOI：
10.3390/ijms23042008
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发表时间：
2022-02-11
影响因子：
5.6
通讯作者：
Allen AR
中科院分区：
文献类型：
--
作者：
Ntagwabira F;Trujillo M;McElroy T;Brown T;Simmons P;Sykes D;Allen AR
早期诊断和治疗的进步提高了乳腺癌的生存率。幸存者报告了认知障碍症状，例如注意力不集中以及学习和记忆缺陷，这显着降低了患者的生活质量。需要额外的疗法来预防这些副作用，并且其确切的作用机制尚未完全阐明。然而，越来越多的证据表明，使用具有抗氧化剂和抗炎特性的神经保护化合物作为保护学习和记忆的工具。在这里，我们检查了胡椒长明 (PL)（一种已知具有抗炎和抗氧化作用的生物碱）在接受阿霉素、环磷酰胺和多西他赛 (TAC) 等常见乳腺癌治疗方案治疗的 16 周龄雌性 C57BL/6J 小鼠中发挥神经保护作用的能力。在社交记忆测试期间，TAC 治疗的小鼠表现出损害，而 TAC/PL 共同治疗的小鼠没有表现出可测量的社交记忆缺陷。蛋白质组学分析表明 ERK1/2 信号传导参与 TAC 和 TAC/PL 联合治疗。还观察到 Nrf2 mRNA 表达减少。 Gria2 mRNA 水平在TAC 处理的小鼠中增加，而在TAC/PL 共同处理的小鼠中减少。在这项研究中，当 PL 与 TAC 共同给药时，通过涉及氧化应激和突触可塑性的多因素机制，可防止社交记忆损伤。
Advances in the early diagnosis and treatment have led to increases in breast cancer survivorship. Survivors report cognitive impairment symptoms such as loss of concentration and learning and memory deficits which significantly reduce the patient’s quality of life. Additional therapies are needed to prevent these side effects and, the precise mechanisms of action responsible are not fully elucidated. However, increasing evidence points toward the use of neuroprotective compounds with antioxidants and anti-inflammatory properties as tools for conserving learning and memory. Here, we examine the ability of piperlongumine (PL), an alkaloid known to have anti-inflammatory and antioxidant effects, to play a neuroprotective role in 16-week-old female C57BL/6J mice treated with a common breast cancer regimen of doxorubicin, cyclophosphamide, and docetaxel (TAC). During social memory testing, TAC-treated mice exhibited impairment, while TAC/PL co-treated mice did not exhibit measurable social memory deficits. Proteomics analysis showed ERK1/2 signaling is involved in TAC and TAC/PL co-treatment. Reduced Nrf2 mRNA expression was also observed. mRNA levels of Gria2 were increased in TAC treated mice and reduced in TAC/PL co-treated mice. In this study, PL protects against social memory impairment when co-administered with TAC via multifactorial mechanisms involving oxidative stress and synaptic plasticity.
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影响因子：
33.6
作者：
Guerriero CJ;Brodsky JL
通讯作者：
Brodsky JL
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Wigstrom, Holger
影响因子：
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作者：
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通讯作者：
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