The effects of long-term locus coeruleus stimulation on amyloid/tau pathology, synaptic plasticity, and memory during Alzheimer's disease progression
长期蓝斑刺激对阿尔茨海默病进展过程中淀粉样蛋白/tau蛋白病理学、突触可塑性和记忆的影响
基本信息
- 批准号:10346110
- 负责人:
- 金额:$ 47.61万
- 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:2022-02-01 至 2027-01-31
- 项目状态:未结题
- 来源:
- 关键词:Abeta clearanceAblationAdultAgeAlzheimer&aposs DiseaseAlzheimer&aposs disease patientAlzheimer&aposs disease therapeuticAlzheimer&aposs disease therapyAmyloidAmyloid beta-ProteinAnimalsAntiinflammatory EffectBehavioralBehavioral ParadigmBrainBrain StemBrain regionCell NucleusCerebral cortexClinicalClinical ResearchClinical TrialsControl GroupsDataDeep Brain StimulationDementiaDeteriorationDevelopmentDiagnosisDisease ProgressionDoseExcisionFocused UltrasoundGenotypeGoalsHigh Pressure Liquid ChromatographyHippocampus (Brain)HumanImmuneImpaired cognitionIn VitroInflammatoryKnowledgeLesionLong-Term EffectsMeasuresMediatingMemoryMemory impairmentMethodsMicrogliaMonoamine OxidaseMoodsMusNeurodegenerative DisordersNeurofibrillary TanglesNeuronsNeurotoxinsNorepinephrineOutcomePathologyPatientsPerformancePhagocytesPhagocytosisPrefrontal CortexProsencephalonRegulationRoleSenile PlaquesSliceSocietiesSourceStructureSymptomsSynaptic plasticitySystemTauopathiesTechnologyTestingThalamic structureTherapeuticTimeVagus nerve structureViralViral VectorWorkcognitive functioncognitive taskelectric fieldexperimental studyhTau Miceimprovedinhibitorinsightknowledge baselocus ceruleus structuremouse modelneural stimulationneuropathologynoradrenaline transporternoradrenergicnorepinephrine systemnovelnovel therapeuticsoffspringoverexpressionpreventreuptaketargeted treatmenttau Proteinstherapeutic targettranslational impactvagus nerve stimulation
项目摘要
Project Summary
The effects of long-term locus coeruleus stimulation on amyloid/tau pathology, synaptic plasticity, and
memory during Alzheimer’s disease progression
Alzheimer’s disease (AD) is a neurodegenerative disease and accounts for up to 80% of all dementia
diagnoses. Despite the immense burden that AD imposes on society, there is currently no effective method to
prevent or treat AD. Severe degeneration of the locus coeruleus (LC) is a ubiquitous hallmark in AD. The LC is
the primary source of norepinephrine (NE) to the whole forebrain and regulates many aspects of normal brain
function. An aberrant form of tau is found in the LC in young healthy adults, making the LC the first region with
AD-like neuropathology in the human brain. Previous work has suggested that NE facilitates the immune-
mediated removal of Aβ through regulation of microglial phagocytosis. In addition, the anti-inflammatory effect
of NE has been demonstrated in many studies. Therefore, the LC-NE system is a promising therapeutic target
in AD. However, the consequences of long-term LC stimulation during AD progression remain unknown. In this
project, using a synthesis of chemogenetic manipulation, retrograde Cre-dependent viral ablation,
immunohistology, and behavioral paradigms, we will examine the effects of long-term locus coeruleus
stimulation on amyloid/tau pathology, synaptic plasticity, and memory in Aβ and tau mouse models. In Aim 1,
we will determine the extent to which long term direct LC stimulation delays the deterioration of memory
function and improves synaptic plasticity. In Aim 2, we will characterize the effects of long-term LC stimulation
on amyloid and tau pathology during AD progression. In Aim 3, we will examine the role of non-uniform LC
degeneration in structure-specific amyloid and tau pathology in the brain. This project will provide much-
needed insight about the extent to which long term LC stimulation mitigates amyloid and tau pathology and
rescues memory functions during AD progress. Such information will likely lead to the development of new
therapeutics for AD that utilize both non-invasive and invasive brain stimulation technologies to directly engage
the LC-NE system.
项目总结
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)
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Qi Wang其他文献
機械インピーダンスの触運動知覚特性
触觉运动的机械阻抗感知特性
- DOI:
- 发表时间:
2011 - 期刊:
- 影响因子:0
- 作者:
Leonard Barolli;Qi Wang;Elis Kulla;Fatos Xhafa;Bexhet Kamo Makoto Takizawa;山本宗;山本雅文;大西 仁・望月 要 - 通讯作者:
大西 仁・望月 要
移動カメラ画像データベースからの消失点軌跡推定処理のMapReduceによる並列化
使用 MapReduce 对移动摄像机图像数据库进行消失点轨迹估计处理的并行化
- DOI:
- 发表时间:
2011 - 期刊:
- 影响因子:0
- 作者:
Leonard Barolli;Qi Wang;Elis Kulla;Fatos Xhafa;Bexhet Kamo Makoto Takizawa;山本宗 - 通讯作者:
山本宗
XMLデータベースにおける構造要約索引を用いたTree Pattern問い合わせ処理方式に関する検討
XML数据库中利用结构化汇总索引的树型模式查询处理方法研究
- DOI:
- 发表时间:
2011 - 期刊:
- 影响因子:0
- 作者:
Leonard Barolli;Qi Wang;Elis Kulla;Bexhet Kamo;Fatos Xhafa Muhammad Younas;山本雅文;朱佳俊 - 通讯作者:
朱佳俊
直線検出に基づく音声検索語検出への音節継続時間の導入
将音节持续时间引入基于直线检测的语音搜索词检测
- DOI:
- 发表时间:
2012 - 期刊:
- 影响因子:0
- 作者:
Leonard Barolli;Qi Wang;Elis Kulla;Bexhet Kamo;Fatos Xhafa Muhammad Younas;山本雅文;朱佳俊;大野哲平,秋葉友良 - 通讯作者:
大野哲平,秋葉友良
A Study on Interactive Search in MOGA with Island Model based on User's Requirements using Visualization in NSP
基于用户需求的MOGA岛模型交互搜索NSP可视化研究
- DOI:
- 发表时间:
2010 - 期刊:
- 影响因子:0
- 作者:
Leonard Barolli;Qi Wang;Elis Kulla;Fatos Xhafa;Bexhet Kamo Makoto Takizawa;山本宗;山本雅文 - 通讯作者:
山本雅文
Qi Wang的其他文献
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{{ truncateString('Qi Wang', 18)}}的其他基金
The effects of long-term locus coeruleus stimulation on amyloid/tau pathology, synaptic plasticity, and memory during Alzheimer's disease progression
长期蓝斑刺激对阿尔茨海默病进展过程中淀粉样蛋白/tau蛋白病理学、突触可塑性和记忆的影响
- 批准号:
10554301 - 财政年份:2022
- 资助金额:
$ 47.61万 - 项目类别:
Noradrenergic and cholinergic mechanisms underlying pupil-linked arousal modulation of thalamic sensory processing
丘脑感觉处理的瞳孔相关唤醒调节的去甲肾上腺素能和胆碱能机制
- 批准号:
10457428 - 财政年份:2021
- 资助金额:
$ 47.61万 - 项目类别:
Noradrenergic and Cholinergic Mechanisms Underlying Pupil-linked Arousal Modulation of Thalamic Sensory Processing
丘脑感觉处理的瞳孔相关唤醒调节的去甲肾上腺素能和胆碱能机制
- 批准号:
10668440 - 财政年份:2021
- 资助金额:
$ 47.61万 - 项目类别:
Noradrenergic and cholinergic mechanisms underlying pupil-linked arousal modulation of thalamic sensory processing
丘脑感觉处理的瞳孔相关唤醒调节的去甲肾上腺素能和胆碱能机制
- 批准号:
10298400 - 财政年份:2021
- 资助金额:
$ 47.61万 - 项目类别:
Noradrenergic and Cholinergic Mechanisms Underlying Pupil-Linked Arousal Modulation of Thalamic Sensory Processing
丘脑感觉处理的瞳孔相关唤醒调节的去甲肾上腺素能和胆碱能机制
- 批准号:
10836252 - 财政年份:2021
- 资助金额:
$ 47.61万 - 项目类别:
Cholinergic contribution to pupil-linked arousal
胆碱能对瞳孔相关唤醒的贡献
- 批准号:
10301014 - 财政年份:2020
- 资助金额:
$ 47.61万 - 项目类别:
The role of the locus coeruleus in mediating pupil-linked arousal
蓝斑在调节瞳孔相关唤醒中的作用
- 批准号:
10063037 - 财政年份:2016
- 资助金额:
$ 47.61万 - 项目类别:
Device to mechanically interrogate tissue and skin across research environments
在研究环境中机械询问组织和皮肤的设备
- 批准号:
8681920 - 财政年份:2011
- 资助金额:
$ 47.61万 - 项目类别:
Device to mechanically interrogate tissue and skin across research environments
在研究环境中机械询问组织和皮肤的设备
- 批准号:
8316130 - 财政年份:2011
- 资助金额:
$ 47.61万 - 项目类别:
Device to mechanically interrogate tissue and skin across research environments
在研究环境中机械询问组织和皮肤的设备
- 批准号:
8515408 - 财政年份:2011
- 资助金额:
$ 47.61万 - 项目类别:
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