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

基本信息

  • 批准号:
    9114087
  • 负责人:
  • 金额:
    $ 55.95万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 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

项目摘要

 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.


项目成果

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Anne Courtney DeVries其他文献

Anne Courtney DeVries的其他文献

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{{ truncateString('Anne Courtney DeVries', 18)}}的其他基金

Mechanism Underlying Sleep Disruption by Mammary Tumors
乳腺肿瘤扰乱睡眠的机制
  • 批准号:
    10651086
  • 财政年份:
    2023
  • 资助金额:
    $ 55.95万
  • 项目类别:
Affective Consequences of Chemotherapy
化疗的情感后果
  • 批准号:
    9788290
  • 财政年份:
    2018
  • 资助金额:
    $ 55.95万
  • 项目类别:
Adverse Consequences of Light at Night for Cerebral Ischemia
夜间光对脑缺血的不良后果
  • 批准号:
    9272450
  • 财政年份:
    2015
  • 资助金额:
    $ 55.95万
  • 项目类别:
Affective Consequences of Chemotherapy
化疗的情感后果
  • 批准号:
    8989060
  • 财政年份:
    2015
  • 资助金额:
    $ 55.95万
  • 项目类别:
Social Modulation of Microglia
小胶质细胞的社会调节
  • 批准号:
    9069534
  • 财政年份:
    2015
  • 资助金额:
    $ 55.95万
  • 项目类别:
Adverse Consequences of Light at Night for Cerebral Ischemia
夜间光对脑缺血的不良后果
  • 批准号:
    9070024
  • 财政年份:
    2015
  • 资助金额:
    $ 55.95万
  • 项目类别:
West Virginia University Stroke COBRE
西弗吉尼亚大学中风 COBRE
  • 批准号:
    10523541
  • 财政年份:
    2014
  • 资助金额:
    $ 55.95万
  • 项目类别:
West Virginia University Stroke COBRE
西弗吉尼亚大学中风 COBRE
  • 批准号:
    10640956
  • 财政年份:
    2014
  • 资助金额:
    $ 55.95万
  • 项目类别:
West Virginia University Stroke COBRE
西弗吉尼亚大学中风 COBRE
  • 批准号:
    10581811
  • 财政年份:
    2014
  • 资助金额:
    $ 55.95万
  • 项目类别:
West Virginia University Stroke COBRE
西弗吉尼亚大学中风 COBRE
  • 批准号:
    10451737
  • 财政年份:
    2014
  • 资助金额:
    $ 55.95万
  • 项目类别:

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