Effect of n-3 fatty acids and sugars on chemotherapy-induced cognitive deficits

n-3 脂肪酸和糖对化疗引起的认知缺陷的影响

• 批准号: 9114087
• 负责人: Anne Courtney DeVries
• 金额: $ 55.95万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-21 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9114087
• 关键词: Address; Adult; Adverse effects; Affect; American; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antineoplastic Agents; Automobile Driving; Biological; Brain; Breast Cancer Patient; Breast Cancer survivor; Cancer Survivor; Chemotherapy-Oncologic Procedure; Cognition; Cognitive; Cognitive deficits; Consumption; Cytokine Activation; Data; Development; Diabetes Mellitus; Diagnosis; Diet; Dietary Practices; Dietary Supplementation; Docosahexaenoic Acids; Dose; Doxorubicin; Drug Combinations; Elderly; Exposure to; Fatty acid glycerol esters; Female; Fiber; Food; Food Processing; Fructose; Glucose; Guidelines; Health; Impaired cognition; In Vitro; Inflammation; Inflammatory; Intake; Life; Link; Lipid Peroxidation; Mammary Neoplasms; Memory; Memory impairment; Microglia; Mus; Neurologic; Neurons; Omega-3 Fatty Acids; Oxidative Stress; Pathway interactions; Performance; Plants; Play; Prevention strategy; Quality of life; Reading; Recommendation; Reporting; Research; Rodent; Rodent Model; Role; Safety; Social Interaction; Staging; Structure; Sucrose; Supplementation; Trauma; United States; Vertebral column; Woman; Work; abstracting; base; brain tissue; cancer surgery; chemotherapy; cognitive change; cognitive function; cognitive performance; cytokine; density; drinking; fatty acid supplementation; fruits and vegetables; improved; macrophage; malignant breast neoplasm; memory process; mouse model; neoplastic cell; neurogenesis; neuroinflammation; prevent; processing speed; protective effect; randomized placebo controlled trial; relating to nervous system; research study; sugar; tumor

 DESCRIPTION (provided by applicant): Effect of omega-3 fatty acid supplementation and added sugars in the diet on chemotherapy-induced cognitive deficits Abstract Women diagnosed with breast cancer (BC) comprises the largest group of cancer survivors in the United States. Chemotherapy used to treat BC has potentially toxic side effects in the brain, adversely affecting verbal fluency, memory and processing speed in up to 30% of women treated. The biological basis of chemotherapy induced cognitive dysfunction is poorly understood and no effective preventative strategies exist. Our preliminary data illustrate that chemotherapy increases oxidative stress, which in turn promotes neuroinflammation and cognitive changes in a mouse model; maintaining mice on high sucrose diets exacerbates the inflammation. In BC survivors, our data suggest that an unhealthy (i.e. high added sugar) diet increases systemic inflammation post-chemotherapy. Supplementing with omega-3 fatty acids (n-3 FAs) is a promising strategy to decrease inflammation and address life-altering cognitive side effects for several reasons: n-3 FAs reduce inflammatory cytokines and lipid peroxidation in rodent models, improve cognition in some older adults, and have established safety and tolerability with chemotherapy. However, high amounts of added sugars in the diet may interfere with the anti-inflammatory effects of n-3 FAs. The primary objective of this proposal is to use a randomized placebo controlled trial to determine the extent to which dietary supplementation with n-3 FAs reduces neuroinflammation and prevents cognitive decline in women receiving chemotherapy after BC surgery, and whether n-3 FAs are more effective in women whose usual diets are lower in added sugars. In addition, we will examine the mechanisms through which chemotherapy impairs cognitive performance and the potential of added sugars to modify the neuroprotective effects of n-3 FAs by including experiments using a translational mouse model that closely approximates the chemotherapy regimen commonly used to treat women with BC. We hypothesize that a low sugar/high n-3 FA diet will reduce neuroinflammation, decreasing inflammatory cytokines and activation of brain macrophages (microglia) in mice, which in turn will lessen chemotherapy-induced cognitive deficits. We further hypothesize that n-3 FA supplementation will decrease the cognitive side effects of chemotherapy in women with BC, and that the reduction in side effects will be greater in women who consume lower levels of added sugars in the diet. Understanding the mechanisms by which chemotherapy causes cognitive changes, the potential exacerbating role of added sugars, and intervening with n-3 FAs to alleviate these deficits are the necessary first steps in establishing an effective preventative strategy for chemotherapy-induced cognitive dysfunction, which could vastly improve quality of life for cancer survivors.

 描述（由申请人提供）：补充 omega-3 脂肪酸和在饮食中添加糖对化疗引起的认知缺陷的影响 摘要 在美国，被诊断患有乳腺癌 (BC) 的女性是接受化疗的最大的癌症幸存者群体。治疗 BC 可能对大脑产生毒副作用，对多达 30% 的女性的语言流畅性、记忆力和处理速度产生不利影响。化疗引起的认知功能障碍的生物学基础尚不清楚，而且目前尚无有效的预防策略。数据表明，化疗会增加氧化应激，进而促进小鼠模型的神经炎症和认知变化；在 BC 幸存者中，维持高蔗糖饮食会加剧炎症，我们的数据表明，不健康（即高添加糖）饮食会增加全身炎症。化疗后的炎症补充 omega-3 脂肪酸 (n-3 FA) 是减少炎症和解决改变生活的认知副作用的有效策略，原因如下： n-3 FA 可以减少啮齿动物模型中的炎症细胞因子和脂质过氧化，改善一些老年人的认知能力，并已确定化疗的安全性和耐受性。然而，饮食中大量添加的糖可能会干扰 n-3 FA 的抗炎作用。该提案的主要目的是使用随机安慰剂对照试验来确定饮食中添加 n-3 FA 能在多大程度上减少 BC 手术后接受化疗的女性的神经炎症和预防认知能力下降，以及是否n-3 FA 对日常饮食中添加糖含量较低的女性更有效。此外，我们将研究化疗损害认知能力的机制，以及添加糖通过包括在内来改变 n-3 FA 的神经保护作用的潜力。使用与治疗 BC 女性常用化疗方案非常相似的转化小鼠模型进行实验，我们努力证明低糖/高 n-3 FA 饮食会减少神经炎症，减少炎症细胞因子和脑巨噬细胞的激活。 （小胶质细胞），这反过来会减轻化疗引起的认知缺陷，我们进一步发现，补充 n-3 FA 将减少 BC 女性化疗的认知副作用，并且副作用的减少在 BC 女性中会更大。了解化疗导致认知变化的机制、添加糖的潜在加剧作用以及使用 n-3 FA 进行干预以缓解这些缺陷是建立有效的认知障碍的必要的第一步。预防策略用于治疗化疗引起的认知功能障碍，这可以极大地改善癌症幸存者的生活质量。