Novel strategy to enrich brain DHA through diet: Potential application for the prevention of Alzheimer's disease
通过饮食丰富大脑 DHA 的新策略:预防阿尔茨海默病的潜在应用
基本信息
- 批准号:10454878
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-04-01 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcetylcholineAffectAgeAlzheimer disease preventionAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAlzheimer&aposs disease pathologyAmericanAnimal ModelAnimalsAnti-Inflammatory AgentsBehaviorBlood - brain barrier anatomyBrainBrain-Derived Neurotrophic FactorCholineClinical TrialsCognitionCognitiveDataDementiaDevelopmentDietDiseaseDisease modelDocosahexaenoic AcidsDocosahexaenoic acid supplementDoseEicosapentaenoic AcidEstersEthanolaminesEuphausiaceaFailureFish OilsGeneral PopulationHeadHydrolysisIntestinal AbsorptionIntestinesLeadLysophosphatidylcholinesLysophospholipidsMemoryMental DepressionMetabolicMusNerve TissueNutraceuticalOilsOmega-3 Fatty AcidsOxidesParkinson DiseasePathologicPatientsPhospholipidsPopulationPost-Traumatic Stress DisordersPrevalencePreventionPrevention strategyRattusRisk FactorsSchizophreniaSerineSymptomsTestingTransgenic MiceTraumatic Brain InjuryTriglyceridesVeteransabsorptionbasebrain tissuecognitive functioncostdietaryeffective therapyeffectiveness testinghigh riskimprovedintestinal barriermouse modelnervous system disorderneuroinflammationneuropathologynovelnovel strategiespreventspatial memorysuccess
项目摘要
Alzheimer’s disease (AD) is the leading cause of dementia, and affects about 5 million
Americans at present. It is projected to afflict 16 million Americans by 2050 and cost the
economy $1.1 trillion. The prevalence of AD is much greater in veterans than in the general
population because of a constellation of risk factors including age, traumatic brain injury,
depression, and PTSD all of which are more prevalent in the veterans. While there is no
effective treatment for AD at present, several studies in animal models have shown beneficial
effects of docosahexaenoic acid (DHA) which is uniquely concentrated in the brain, and is
known to be essential for its function. However, clinical trials using the currently available DHA
supplements (fish oil, krill oil, algal oil, ethyl esters etc) to improve cognitive function in patients
have been disappointing. We postulate that this failure is due to the inability of these
supplements to enrich brain DHA at the recommended safe doses, because they are all
absorbed in the form of triacylglycerol (TAG) rather than in the phospholipid form required by
the transporter at the blood brain barrier (BBB). We have recently demonstrated that dietary
DHA in the form of lysophosphatidylcholine (LPC), which is absorbed in the phospholipid form,
not only enriches brain DHA at low doses, but also improves cognition and spatial memory in
normal mice. The current proposal will explore the potential of LPC and other lysophospholipids
(LPL) in enriching brain DHA and in the prevention of AD in a mouse model of the disease.
In Aim 1, we will test the hypothesis that dietary DHA-lysophospholipids (LPL) are superior to
either TAG-DHA (as in fish oil) or natural phospholipid DHA (as in krill oil) in enriching the brain
DHA and improving cognitive function in normal mice. In addition, the effect of the polar head
group of the LPL (choline, ethanolamine, or serine), as well as the effect of eicosapentaenoic
acid (EPA) will be determined, to identify the most efficient LPL for improving the brain function.
In Aim 2, we will test the hypothesis that treatment with a low dose of LPL-DHA (identified in
Aim 1) will prevent or delay the development of AD in a double transgenic mouse model of AD.
Three-month-old APPswe/PS1ΔE9 mice will be treated with either LPL-DHA or TAG-DHA at a
daily dose of 40 mg DHA/kg for 9 months, and the effects on cognitive behavior, memory, and
neuropathology will be determined. It is anticipated that LPL-DHA, but not TAG-DHA would
alleviate the pathological symptoms of AD at these low doses.
In Aim 3, we will determine the mechanisms underlying the beneficial effects of LPL-DHA,
compared to the currently available supplements of DHA, in enriching brain DHA and in
improving brain function. The hypotheses to be tested include: a) that the metabolic advantage
of LPL-DHA is due its ability to cross both the intestinal barrier and blood brain barrier, b) that
LPL-DHA is more anti-inflammatory than free DHA, c) that LPL-DHA is oxidized less rapidly in
the brain than free DHA, and d) LPC-DHA contributes choline, the essential component of
acetylcholine, in addition to DHA, which has pluripotent effects on brain function and AD
development.
Successful completion of these studies could lead to a novel nutraceutical strategy for the
prevention and treatment of AD, as well as other neuro-inflammatory diseases in the population
in general, and in the veterans in particular.
阿尔茨海默病(AD)是痴呆症的主要原因,约有500万人受到影响
项目成果
期刊论文数量(0)
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PAPASANI V SUBBAIAH其他文献
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{{ truncateString('PAPASANI V SUBBAIAH', 18)}}的其他基金
Novel strategy to enrich brain DHA through diet: Potential application for the prevention of Alzheimer's disease
通过饮食丰富大脑 DHA 的新策略:预防阿尔茨海默病的潜在应用
- 批准号:
10265364 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Novel strategy to enrich brain DHA through diet: Potential application for the prevention of Alzheimer's disease
通过饮食丰富大脑 DHA 的新策略:预防阿尔茨海默病的潜在应用
- 批准号:
10663811 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Novel strategy to enrich brain DHA through diet: Potential application for the prevention of Alzheimer's disease
通过饮食丰富大脑 DHA 的新策略:预防阿尔茨海默病的潜在应用
- 批准号:
9922660 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Molecular Form of Dietary DHA and its Bioavailability for the Brain
膳食 DHA 的分子形式及其对大脑的生物利用度
- 批准号:
8755224 - 财政年份:2014
- 资助金额:
-- - 项目类别:
Molecular Form of Dietary DHA and its Bioavailability for the Brain
膳食 DHA 的分子形式及其对大脑的生物利用度
- 批准号:
8900973 - 财政年份:2014
- 资助金额:
-- - 项目类别:
Role of Membrane Modifications in the Bioactivities of Conjugated Linoleic Acids
膜修饰在共轭亚油酸生物活性中的作用
- 批准号:
8803247 - 财政年份:2013
- 资助金额:
-- - 项目类别:
Role of Membrane Modifications in the Bioactivities of Conjugated Linoleic Acids
膜修饰在共轭亚油酸生物活性中的作用
- 批准号:
8974264 - 财政年份:2013
- 资助金额:
-- - 项目类别:
Role of Membrane Modifications in the Bioactivities of Conjugated Linoleic Acids
膜修饰在共轭亚油酸生物活性中的作用
- 批准号:
8542103 - 财政年份:2013
- 资助金额:
-- - 项目类别:
Role of Membrane Modifications in the Bioactivities of Conjugated Linoleic Acids
膜修饰在共轭亚油酸生物活性中的作用
- 批准号:
8727969 - 财政年份:2013
- 资助金额:
-- - 项目类别:
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