Effects of binge ethanol on neuroinflammation and neurodegeneration with high fat diets
暴饮乙醇对高脂肪饮食引起的神经炎症和神经变性的影响
基本信息
- 批准号:10668068
- 负责人:
- 金额:$ 39.19万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-03 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:AbbreviationsAdaptor Signaling ProteinAdipose tissueAffectAlcohol consumptionAlcoholsAmygdaloid structureAmyloid beta-Protein PrecursorAnimal ModelAnti-Inflammatory AgentsAntibodiesAtrophicAttenuatedBioinformaticsBlood alcohol level measurementBrainCX3CL1 geneCalcium BindingCell membraneCerebral cortexChronicDevelopmentDietDiseaseDisease ProgressionDocosahexaenoic AcidsDocosahexaenoic acid supplementElderlyEssential Fatty AcidsEthanolExhibitsFatty AcidsFatty acid glycerol estersHIVHIV-1HIV/AIDSHigh Fat DietHippocampusHypothalamic structureImmuneImmunofluorescence ImmunologicInflammationKnowledgeLaboratoriesLicensingLigandsLinkMediatingMediatorMicrogliaMolecularMusN-3 polyunsaturated fatty acidNerve DegenerationNeurodegenerative DisordersNeurogliaNutrientObesityOutcome StudyPathologyPathway AnalysisPatientsPatternPolyunsaturated Fatty AcidsPrevalenceProductionPropertyProteinsRat TransgeneRattusReportingResearchRisk FactorsSaturated Fatty AcidsSolidStainsTestingTherapeuticUnited Statesalcohol effectantiretroviral therapyattenuationbinge drinkingcerebral atrophychemokineclinically relevantcombinatorialdiet-induced obesitydrinkingfeedingfluoro jadehuman modelin vivoinflammatory markerionizationknowledge baselocus ceruleus structuremild cognitive impairmentmouse modelneuroinflammationneuron componentneuroprotectionpreventsystemic inflammatory responsetranscriptometranscriptome sequencingwhite matter
项目摘要
Abstract: Obesity has been associated with neuroinflammation and neurodegeneration. Binge drinking (BD)
has also been reported to lead to neuroinflammation and brain atrophy. Moreover, our bioinformatics analysis
using Ingenuity Pathway Analysis (IPA) licensed from QIAGEN confirmed that ethanol (EtOH) and obesity induce
neuroinflammation. Studies have suggested alcohol and obesit
disease (AD) with neuroinflammation and neurodegeneration as the central link. We also conducted IPA analysis
to examine the paths from alcohol and obesity to AD. Both alcohol and obesity were linked to AD with alcohol
exhibiting an overall activation of AD development. These studies also revealed a critical knowledge gap on
binge EtOH (BE) augmentation of obesity-induced neuroinflammation and neurodegeneration. As essential
nutrients and fundamental components of neuronal and glial cell membranes, n-3 polyunsaturated fatty acids
(PUFAs) have been reported with anti-inflammatory properties and beneficial effects in elderly with mild cognitive
impairment. Our laboratory used 5-week 3-day each week BE to mimic BD over the weekends and found that
docosahexaenoic acid (DHA; 22:6n-3), a PUFA, ameliorates BE-induced inflammation in HIV-1 transgenic rats,
an animal model for HIV/AIDS patients on combination antiretroviral therapy. Using IPA, we found that n-3
PUFAs may decrease the production of amyloid precursor protein (APP), a key molecule associated with the
onset and progression of AD.
Taken these solid premises together, we hypothesize that BE may augment obesity-induced
neuroinflammation and neurodegeneration while n-3 PUFAs may attenuate BE-induced
neuroinflammation and neurodegeneration. To test these hypotheses, we will use a diet-induced-obesity
mouse model by feeding C57BL/6J mice with control 10 kcal% fat diet (CD), DHA-supplemented CD (DCD), 45%
kcal% high fat diet (HFD), DHA-supplemented 45 kcal% high fat diet (DHFD) and propose two aims. Aim 1 is to
examine the effects of BE on neuroinflammation and neurodegeneration at the cellular level in the brain of mice
fed with CD, DCD, HFD, or DHFD with or without BE using immunofluorescence staining and Fluoro-Jade B
staining. Aim 2 is to examine the effects of BE on neuroinflammation and neurodegeneration at the molecular
level in the brain of mice fed with CD, DCD, HFD, or DHFD with or without BE using RNA-sequencing, antibody
arrays, and bioinformatic analysis.
These studies are highly significant with clinical relevance. Successful completion of these studies will
shed light on whether and how BE may augment obesity-induced neuroinflammation and neurodegeneration
and on whether and how n-3 PUFAs may affect BE-induced neuroinflammation and neurodegeneration. The
study outcomes shall shift the paradigm regarding interaction between BD and diet-mediated pathologies
including characterization of n-3 PUFAs in preventing the onset and progression of AD pathologies.
摘要:肥胖与神经炎症和神经变性有关。暴饮暴食(BD)
据报道,还导致神经炎症和脑萎缩。而且,我们的生物信息学分析
使用Qiagen许可的Ingenuity途径分析(IPA)证实乙醇(ETOH)和肥胖症诱导
神经炎症。研究表明酒精和肥胖症
具有神经炎症和神经退行性的疾病(AD)作为中心联系。我们还进行了IPA分析
检查从酒精和肥胖到AD的路径。酒精和肥胖都与酒精有关
表现出广告开发的总体激活。这些研究还揭示了有关的关键知识差距
肥胖诱导的神经炎症和神经变性的狂热ETOH(BE)增强。至关重要
神经元和神经胶质细胞膜的营养和基本成分,N-3多不饱和脂肪酸
(PUFAS)据报道具有抗炎特性和对老年人的有益作用
损害。我们的实验室每周使用5周的3天,是在周末模仿BD,发现
Docosahexaenoic Acid(DHA; 22:6n-3),PUFA,可以改善HIV-1转基因大鼠的炎症,炎症,
HIV/AIDS患者的动物模型进行抗逆转录病毒疗法。使用IPA,我们发现N-3
PUFA可能会降低淀粉样蛋白前体蛋白(APP)的产生,这是一种与之相关的关键分子
AD的发作和进展。
我们假设将这些坚实的前提放在一起,可能会增加肥胖引起的
神经炎症和神经变性,而N-3 PUFA可能会诱导
神经炎症和神经变性。为了检验这些假设,我们将使用饮食引起的肥胖
通过对照10 kcal%脂肪饮食(CD)喂食C57BL/6J小鼠的小鼠模型,DHA补充CD(DCD),45%
KCAL%高脂肪饮食(HFD),DHA供电的45 kcal%高脂肪饮食(DHFD),并提出了两个目标。目标1是
检查BE对小鼠大脑细胞水平上神经炎症和神经退行性的影响
用CD,DCD,HFD或DHFD喂食或不使用免疫荧光染色和氟jade B
染色。 AIM 2是检查BE对分子神经炎症和神经退行性的影响
用CD,DCD,HFD或DHFD喂养的小鼠的大脑中的水平,或者不使用RNA序列,抗体
阵列和生物信息学分析。
这些研究具有临床相关性非常重要。这些研究的成功完成将
揭示是否以及如何增加肥胖引起的神经炎症和神经变性
以及n-3 PUFA是否可能影响神经炎症和神经变性。这
研究结果应改变有关BD和饮食介导的病理之间相互作用的范式
包括对N-3 PUFA的表征,以防止AD病理的发作和进展。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
SULIE L. CHANG其他文献
SULIE L. CHANG的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('SULIE L. CHANG', 18)}}的其他基金
Involvement of microglial α7AChR in binge alcohol modulation of gut dysbiosis
小胶质细胞α7AChR参与酗酒调节肠道菌群失调
- 批准号:
10705750 - 财政年份:2022
- 资助金额:
$ 39.19万 - 项目类别:
Involvement of microglial α7AChR in binge alcohol modulation of gut dysbiosis
小胶质细胞α7AChR参与酗酒调节肠道菌群失调
- 批准号:
10527744 - 财政年份:2022
- 资助金额:
$ 39.19万 - 项目类别:
Modulation of OPRM1 alternative splicing by morphine and HIV-1 Nef
吗啡和 HIV-1 Nef 对 OPRM1 选择性剪接的调节
- 批准号:
10654016 - 财政年份:2021
- 资助金额:
$ 39.19万 - 项目类别:
Methylation in binge ethanol-induced spleen atrophy in adolescent rats
青春期大鼠暴食乙醇引起的脾萎缩的甲基化
- 批准号:
10400702 - 财政年份:2018
- 资助金额:
$ 39.19万 - 项目类别:
Immunomodulation of nicotine in HIV-1Tg rat brain
尼古丁对 HIV-1Tg 大鼠脑的免疫调节作用
- 批准号:
9897503 - 财政年份:2018
- 资助金额:
$ 39.19万 - 项目类别:
Immunomodulation of nicotine in HIV-1Tg rat brain
尼古丁对 HIV-1Tg 大鼠脑的免疫调节作用
- 批准号:
10378566 - 财政年份:2018
- 资助金额:
$ 39.19万 - 项目类别:
Methylation in binge ethanol-induced spleen atrophy in adolescent rats
青春期大鼠暴食乙醇引起的脾萎缩的甲基化
- 批准号:
10155374 - 财政年份:2018
- 资助金额:
$ 39.19万 - 项目类别:
Alcohol-induced Impairment of Endothelial Cell Recovery
酒精引起的内皮细胞恢复损伤
- 批准号:
9238541 - 财政年份:2017
- 资助金额:
$ 39.19万 - 项目类别:
Involvement of TRP Channels in Ethanol Concentration-Dependent Effects on Immune
TRP 通道参与乙醇浓度依赖性免疫效应
- 批准号:
8740695 - 财政年份:2014
- 资助金额:
$ 39.19万 - 项目类别:
Involvement of TRP Channels in Ethanol Concentration-Dependent Effects on Immune
TRP 通道参与乙醇浓度依赖性免疫效应
- 批准号:
8936414 - 财政年份:2014
- 资助金额:
$ 39.19万 - 项目类别:
相似海外基金
Measurement and Prediction of Endothelial Cross-family Signaling
内皮跨家族信号传导的测量和预测
- 批准号:
10689341 - 财政年份:2022
- 资助金额:
$ 39.19万 - 项目类别:
Measurement and Prediction of Endothelial Cross-family Signaling
内皮跨家族信号传导的测量和预测
- 批准号:
10672552 - 财政年份:2022
- 资助金额:
$ 39.19万 - 项目类别:
Systems analysis and prediction of endothelial cross-family signaling
内皮跨家族信号传导的系统分析和预测
- 批准号:
10317179 - 财政年份:2021
- 资助金额:
$ 39.19万 - 项目类别:
Hepatic metabolic reprogramming drives pancreatic cancer cachexia
肝脏代谢重编程导致胰腺癌恶病质
- 批准号:
10210248 - 财政年份:2020
- 资助金额:
$ 39.19万 - 项目类别:
Hepatic metabolic reprogramming drives pancreatic cancer cachexia
肝脏代谢重编程导致胰腺癌恶病质
- 批准号:
10435494 - 财政年份:2020
- 资助金额:
$ 39.19万 - 项目类别: