Changes in Cerebrovascular Function with Aging in Normal and AD Brain
正常脑和 AD 脑中脑血管功能随衰老的变化
基本信息
- 批准号:10334548
- 负责人:
- 金额:$ 48.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-03-01 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAddressAgeAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease brainAlzheimer&aposs disease modelAmyloidAmyloid depositionAmyloidosisAnimalsArteriesAstrocytesBiologicalBloodBlood - brain barrier anatomyBlood VesselsBlood capillariesBlood flowCell SeparationCerebral Amyloid AngiopathyCerebrovascular CirculationCerebrovascular systemCerebrumChronicControl AnimalDataDepositionDinoprostoneDiseaseEndotheliumFunctional disorderGene ExpressionGene ProteinsGenesGeneticGenomicsGliosisHealthHippocampus (Brain)HyperemiaImpairmentLasersLightLongevityMagnetismMaintenanceModelingMusPathogenesisPathologicPeptide HydrolasesPericytesPositioning AttributeProcessProteinsProteomeProteomicsResearchRoleSecondary toSenile PlaquesSex DifferencesSignal TransductionSmooth MuscleSpecific qualifier valueStructureSurfaceTight JunctionsTimeToxic effectTracerTransgenic MiceTreesVibrissaeage relatedamyloid pathologyarteriolecell typecerebrovascularclinically relevantexperimental studyfamilial Alzheimer diseasefunctional declinefunctional disabilitygender differencehealthy agingimprovedin vivoinnovationmouse modelmultiphoton imagingneurotoxicneurovascular couplingneurovascular unitnormal agingnovelpathological agingprotein expressionsextranscriptometranscriptome sequencing
项目摘要
The surface of cerebral blood vessels is covered nearly entirely by astrocyte processes called endfeet. Astrocytic
endfeet are perfectly positioned to interact with the endothelial vessel walls, and, where present, the surrounding
smooth muscles or pericytes. Through the release of vasoactive molecules such as PGE2, astrocytes regulate local
blood flow (functional hyperemia) and through the release of angiogenic signals induce tight junction proteins that
form the blood brain barrier (BBB). Consequently, any condition that compromises the structure or function of the
endfoot can cause impaired blood flow or impairments of the BBB. In a previous study using a model of familial
Alzheimer disease (AD; hAPPJ202), we1 showed vascular amyloid deposits aggregating between the astrocytic
endfeet and the vessel wall and such amyloid laden vessels showed an impaired ability to regulate vascular tone
and blood flow upon stimulation. Preliminary data suggests that where amyloid deposits are present on vessels
and endfeet displaced, focal breaches in the BBB occur. However, the causative role of vascular amyloid versus
structural and functional changes of astrocytic endfeet in this context are not known. Indeed, while reduced blood
flow and weakening of the BBB have been demonstrated with aging, the specific role of astrocytes in vessel health
over the lifespan are largely unknown. We hypothesize that normal aging is associated with progressive dysfunction
of astrocytic endfeet causing impairment in functional hyperemia and gradual weakening of the BBB. These agerelated
impairments are accelerated in the AD brain as a function of amyloid being functionally “toxic” to
astrocytes and/or pericytes. Here we propose to use two genetic mouse model of familial AD (hAPPJ202, APP233)
with robust vascular amyloidosis1,4 and progressive gliosis1, and age matched control animals to study the specific
role of astrocytes and pericytes to maintain vessel health and function during normal and pathological aging.
No prior studies have examined specific functional impairments of astrocyte endfeet in normal aging compared to
AD, and a possible specific gliotoxic effect of amyloid; two conceptually innovative ideas. State of the art chronic in
vivo multi-photon imaging will be applied to well established transgenic mouse models of AD with vascular
amyloidosis. Combined with novel cell-type specific genomics and proteomics, this proposal will shed light on
astrocyte specific changes in gene and protein expression over the time course of AD (and normal aging) with specific
analysis of gender differences.
脑血管表面几乎完全被称为终足的星形胶质突起覆盖。星形
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 }}
HARALD W SONTHEIMER其他文献
HARALD W SONTHEIMER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('HARALD W SONTHEIMER', 18)}}的其他基金
Changes in Cerebrovascular Function with Aging in Normal and AD Brain
正常脑和 AD 脑中脑血管功能随衰老的变化
- 批准号:
10543141 - 财政年份:2020
- 资助金额:
$ 48.58万 - 项目类别:
Changes in Cerebrovascular Function with Aging in Normal and AD Brain
正常脑和 AD 脑中脑血管功能随衰老的变化
- 批准号:
10438950 - 财政年份:2020
- 资助金额:
$ 48.58万 - 项目类别:
Regulation of Amino-acid Transport in Human Gliomas
人类神经胶质瘤中氨基酸运输的调节
- 批准号:
10393364 - 财政年份:2018
- 资助金额:
$ 48.58万 - 项目类别:
Regulation of Amino-acid Transport in Human Gliomas
人类神经胶质瘤中氨基酸运输的调节
- 批准号:
10064133 - 财政年份:2018
- 资助金额:
$ 48.58万 - 项目类别:
Regulation of Amino-acid Transport in Human Gliomas
人类神经胶质瘤中氨基酸运输的调节
- 批准号:
10321925 - 财政年份:2018
- 资助金额:
$ 48.58万 - 项目类别:
Regulation of Amino-acid Transport in Human Gliomas
人类神经胶质瘤中氨基酸运输的调节
- 批准号:
10520044 - 财政年份:2018
- 资助金额:
$ 48.58万 - 项目类别:
Amino Acid Transport and the Biology of Human Gliomas
氨基酸转运和人类神经胶质瘤的生物学
- 批准号:
9131426 - 财政年份:2015
- 资助金额:
$ 48.58万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 48.58万 - 项目类别:
Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 48.58万 - 项目类别:
Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 48.58万 - 项目类别:
Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 48.58万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 48.58万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 48.58万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 48.58万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 48.58万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 48.58万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 48.58万 - 项目类别:
Research Grant














{{item.name}}会员




