Division of Radiation Health, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR 72205, USA.
Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR 72205, USA.
Int J Mol Sci. 2022 Feb 11;23(4):2008. doi: 10.3390/ijms23042008.
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.
早期诊断和治疗的进展导致乳腺癌存活率的提高。幸存者报告有认知障碍症状，如注意力不集中、学习和记忆缺陷，这显著降低了患者的生活质量。需要额外的治疗方法来预防这些副作用，而负责这些副作用的确切机制尚未完全阐明。然而，越来越多的证据表明，使用具有抗氧化和抗炎特性的神经保护化合物作为保存学习和记忆的工具。在这里，我们研究了胡椒碱（PL）在接受阿霉素、环磷酰胺和多西紫杉醇（TAC）常见乳腺癌方案治疗的 16 周龄雌性 C57BL/6J 小鼠中发挥神经保护作用的能力，PL 是一种已知具有抗炎和抗氧化作用的生物碱。在社交记忆测试中，TAC 处理的小鼠表现出损伤，而 TAC/PL 共同处理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 信号参与了 TAC 和 TAC/PL 共同处理。还观察到 Nrf2 mRNA 表达减少。在 TAC 处理的小鼠中 Gria2 的 mRNA 水平增加，而在 TAC/PL 共同处理的小鼠中减少。在这项研究中，PL 通过涉及氧化应激和突触可塑性的多因素机制与 TAC 共同给药可防止社交记忆损伤。
