Impact of Prenatal alcohol on Alzheimer's disease related pathology and cognitive impairment
产前酒精对阿尔茨海默病相关病理和认知障碍的影响
基本信息
- 批准号:10387300
- 负责人:
- 金额:$ 21.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-02-10 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAdultAffectAgeAge-MonthsAgingAlcohol abuseAlcoholismAlcoholsAlzheimer&aposs DiseaseAlzheimer&aposs disease pathologyAlzheimer&aposs disease riskAmericanAnatomyAnimal ModelAppearanceAreaAstrocytosisBehaviorBehavioralBehavioral AssayBiologicalBiological AssayBlood VesselsBlood flowBrainCardiovascular DiseasesCardiovascular systemCaringCephalicCerebrovascular DisordersChronicCognitive deficitsCollaborationsDataDementiaDiseaseDisease susceptibilityEncephalitisExhibitsExonsExposure toFemaleFetal Alcohol ExposureFetal Alcohol Spectrum DisorderFirst Pregnancy TrimesterFoundationsFunctional disorderFutureGoalsHealthHeart HypertrophyHistologicHumanHuman Amyloid Precursor ProteinHypertensionImpaired cognitionImpairmentIndividualInflammationInstitutesInterventionKidney FailureKnowledgeLesionLifeLife ExperienceLinkLongevityMaternal ExposureMeasuresMental DepressionMetabolicMetabolic DiseasesMissionModelingMusMutationNerve DegenerationNeurocognitive DeficitNeurodegenerative DisordersNeurofibrillary TanglesNeurologicNon-Insulin-Dependent Diabetes MellitusOutcome StudyPathogenicityPathologyPersonsPhenotypePredispositionPremature MortalityPremature aging syndromeRattusRecording of previous eventsRecovery of FunctionReportingResearch PersonnelRiskRisk FactorsRodentRodent ModelSenile PlaquesSocial InteractionSwedish mutationTeenagersTestingTransgenesTransgenic OrganismsUltrasonographyage relatedalcohol preventionalcohol related consequencesbehavioral impairmentcerebrovascularclinical carecognitive functiondementia riskdepressive symptomsdisabilitydisorder riskearly life adversityearly onsetexperiencefamilial Alzheimer diseasefetalhypertensivehypoperfusioninnovationischemic injurymalemiddle agemouse modelneurobehavioralnovelobject recognitionoffspringprenatalpresenilin-1socialtrendvaporvirtualyoung adult
项目摘要
Project Summary:
Persons with fetal alcohol spectrum disorders (FASD) experience life-long neurocognitive deficits as well as
social and adaptive dysfunction, but we know virtually nothing about their health as they age. We recently
reported that prenatal alcohol-exposure (PAE) resulted in long-term alteration in cranially-directed blood flow
and reduced recovery of function after an acute ischemic injury in adulthood. This suggests that PAE is an
important risk factor for cerebrovascular diseases and consequently, for dementia and Alzheimer's disease
(AD). Young PAE rats also exhibit cognitive deficits and importantly, increased depression-related behaviors
which are early predictors of AD. Therefore, in these studies, we will utilize the transgenic TgF344-AD rat
which develops AD pathology in aging, to test the hypothesis that PAE will accelerate cerebro-vascular
impairment, behavioral dysfunction and the accumulation of AD-related brain lesions, leading to premature
aging. Moreover, we will specifically test whether male and female PAE offspring differ in their accumulation
of AD-related anatomical and neurobehavioral pathology. We will implement a vapor-chamber model of
repeated PAE, to achieve consistent binge-like maternal exposure episodes, spanning the fetal neurogenic
period. PAE and control offspring will be assessed from young adults to 15 months of age, by ultrasound
imaging of cranially directed blood flow, by a panel of behavioral assays for cognitive dysfunction and
depression-like phenotypes, as well as a panel of histological assays for AD pathology.
The investigators have a history of collaboration and application of experimental rigor in their areas of
complementary expertise in models of aging and PAE, which supports the feasibility of the proposed studies.
These studies are significant because they address a critical knowledge gap about the link between early life
adversity, i.e., PAE, and the onset of AD. We expect that, if these studies do link PAE to accelerated AD
pathology, they will help redefine FASD as a disorder of premature aging and strengthen the premise for
investigating mechanisms that link PAE to aging, as well as interventions that decouple this linkage.
项目总结:
患有胎儿酒精谱系障碍(FASD)的人会经历终生的神经认知缺陷以及
社交和适应性障碍,但随着年龄的增长,我们几乎对他们的健康状况一无所知。我们最近
报道称,产前酒精暴露(PAE)会导致颅脑血流量的长期改变
以及成年后急性缺血性损伤后功能恢复的减慢。这表明PAE是一种
脑血管疾病以及痴呆症和阿尔茨海默病的重要危险因素
(Ad)。年轻的PAE大鼠也表现出认知缺陷,更重要的是,抑郁相关行为增加
这些都是AD的早期预测指标。因此,在这些研究中,我们将利用转基因TgF344-AD大鼠
它在衰老过程中发展AD病理,以验证PAE将加速脑血管的假设
损害、行为功能障碍和AD相关脑部损害的积累,导致早产
衰老。此外,我们还将专门测试雄性和雌性PAE后代在积累方面是否存在差异
与AD相关的解剖学和神经行为病理学。我们将实施一个蒸汽室模型
重复PAE,以实现持续的暴饮式母体暴露发作,跨越胎儿神经源性
句号。PAE和对照后代将从年轻的成年人到15个月大的婴儿通过超声波进行评估
由一组认知功能障碍和行为分析小组进行的颅脑定向血流成像
抑郁症的表型,以及AD病理的一组组织学分析。
研究人员在他们的领域中有合作和应用实验严谨性的历史
在老龄化和PAE模型方面的互补专业知识,这支持拟议研究的可行性。
这些研究具有重要意义,因为它们解决了关于早期生活之间联系的关键知识差距
逆境,即PAE,以及AD的发病。我们预计,如果这些研究确实将PAE与加速AD联系起来
病理学,它们将有助于将FASD重新定义为一种过早衰老的疾病,并加强
研究将PAE与衰老联系起来的机制,以及解除这种联系的干预措施。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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专利数量(0)
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{{ truncateString('Rajesh C Miranda', 18)}}的其他基金
Impact of Prenatal alcohol on Alzheimer's disease related pathology and cognitive impairment
产前酒精对阿尔茨海默病相关病理和认知障碍的影响
- 批准号:
10570173 - 财政年份:2022
- 资助金额:
$ 21.41万 - 项目类别:
Prenatal alcohol and stroke susceptibility in the aging adult with FASD
患有 FASD 的老年人的产前酒精和中风易感性
- 批准号:
10396634 - 财政年份:2018
- 资助金额:
$ 21.41万 - 项目类别:
Prenatal alcohol and stroke susceptibility in the aging adult with FASD
患有 FASD 的老年人的产前酒精和中风易感性
- 批准号:
9915821 - 财政年份:2018
- 资助金额:
$ 21.41万 - 项目类别:
Prenatal alcohol and stroke susceptibility in the aging adult with FASD
患有 FASD 的老年人的产前酒精和中风易感性
- 批准号:
10172800 - 财政年份:2018
- 资助金额:
$ 21.41万 - 项目类别:
Prenatal microRNA neuro-therapeutics for fetal alcohol exposure
针对胎儿酒精暴露的产前 microRNA 神经疗法
- 批准号:
9240564 - 财政年份:2016
- 资助金额:
$ 21.41万 - 项目类别:
Prenatal microRNA neuro-therapeutics for fetal alcohol exposure
针对胎儿酒精暴露的产前 microRNA 神经疗法
- 批准号:
9044875 - 财政年份:2016
- 资助金额:
$ 21.41万 - 项目类别:
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