Disambiguating natural aging from Alzheimer's disease through changes in oral neuromechanics
通过改变口腔神经力学来消除自然衰老与阿尔茨海默病的关系
基本信息
- 批准号:10634762
- 负责人:
- 金额:$ 138.89万
- 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:2020-09-15 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
PROJECT SUMMARY
Many age-related oral health problems, such as masticatory dysfunction, dysphagia, periodontal disease, and tooth loss
have been associated with Alzheimer’s disease (AD). How cortical and biomechanical changes in oromotor behavior
contribute to the onset and progression of AD and age-related dementias (ARD) are widely unknown. This is largely
because of a fundamental gap in understanding the neuromechanical processes, at the level of large-scale activity of single
neurons and neuronal networks, that underlie healthy aging. This represents an important problem because until they
are understood, the cortical mechanisms underlying pathological aging in AD/ARD will remain largely incomprehensible.
The goal of the proposed research is to investigate changes in the orofacial sensorimotor-cognitive neuronal network that
underlie healthy age-related sensorimotor changes and how these cortical correlates are affected by absent sensory inputs
to oral structures and by the presence of AD-like impairments (‘pathological aging’) in old rhesus macaques. The central
hypothesis is that differential patterns of the dynamics of large-scale neural activity and connectivity in the orofacial
sensorimotor cortex (OSMcx) and the ventrolateral frontal cortex (VLFcx) will help disambiguate healthy and pathological
aging. This hypothesis will be tested by pursuing three specific aims: (1) to identify the neuronal correlates of healthy age-
related changes in feeding behavior, (2) to identify changes in cortical representations of oral somatosensation following
sensory nerve block, and (3) to identify changes in neuronal responses and cortical interactions in OSMcx-VLFcx networks
following drug-induced AD-like impairments. Thus, we can evaluate and compare the added burden of sensory loss and
AD-like impairments on aging. The proposed research uses an innovative approach that leverages the unique sensory
innervation of the oral region by different cranial nerves and the use of a pharmacological model to induce AD-like
impairments in old rhesus macaques. We will record cortical activity from multiple chronically implanted microelectrode
arrays in OSMcx-VLFcx simultaneously with 3D tracking of tongue and jaw kinematics using biplanar videoradiography and
the XROMM workflow (X-ray Reconstruction of Moving Morphology) while young and old subjects engage in natural
feeding behavior. The proposed research is significant for (1) defining cortical, biomechanical, and immunohistological
profiles of healthy and pathological aging, (2) determining potential contributing factors to the onset and progression of
AD, and (3) identifying cortical regions that are vulnerable to AD. Using old rhesus macaques has direct translational value
to evaluate potential avenues for pharmacological or cortical therapies for AD. The knowledge gained from the proposed
study has important implications for earlier identification of individuals with chronic oral health issues who may be at risk
for developing AD or ARDs. It may also inform the development of more effective interventions focused on enhancing oral
health outcomes in this group and thus preventing the onset or allaying the progression of AD or ARD.
项目摘要
许多与年龄有关的口腔健康问题,例如咀嚼功能障碍,吞咽困难,牙周疾病和牙齿脱落
与阿尔茨海默氏病(AD)有关。皮质和生物力学如何改变Oromotor行为
有助于AD和与年龄相关的痴呆症(ARD)的发作和进展,这是广泛的未知。这很大程度上
由于理解神经力学过程的根本差距
神经元和神经元网络是健康衰老的基础。这代表了一个重要的问题,因为直到他们
可以理解,AD/ARD中病理老化的皮质机制将在很大程度上难以理解。
拟议的研究的目的是调查口腔感觉运动神经元网络的变化,这些变化
基础健康与年龄相关的感觉运动变化以及这些皮质相关性如何受到感觉输入的影响
到口服结构,并通过旧恒河猕猴中存在类似AD的障碍(“病理老化”)。中央
假设是大规模神经元活动和连通性动力学的差异模式
感觉运动皮层(OSMCX)和腹外侧额叶皮层(VLFCX)将有助于消除健康和病理的歧义
老化。该假设将通过追求三个具体目标来检验:(1)确定健康年龄的神经元相关性 -
喂养行为的相关变化,(2)以确定口服体验的皮质表示的变化
感觉神经阻滞和(3)确定OSMCX-VLFCX网络中神经元反应和皮质相互作用的变化
遵循药物引起的广告样障碍。这,我们可以评估和比较感官丧失的燃烧和
关于衰老的广告状障碍。拟议的研究使用一种创新的方法来利用独特的感官
通过不同的颅神经和使用药物模型诱导AD样
旧恒河猕猴的障碍。我们将记录来自多个慢性植入微电极的皮质活性
只需使用Biplanar视频摄影和下颌运动学的3D跟踪,在OSMCX-VLFCX中进行阵列
Xromm工作流程(X射线移动形态的重建),而老年人则自然参与
喂养行为。拟议的研究对于(1)定义皮质,生物力学和免疫组织学很重要
健康和病理衰老的特征,(2)确定潜在的促成因素
AD和(3)识别容易受到AD的皮质区域。使用旧恒河猕猴具有直接的翻译价值
评估AD药物或皮质疗法的潜在途径。从拟议中获得的知识
研究对可能有危险的慢性口腔健康问题的个体的早期识别具有重要意义
用于开发广告或ARDS。它还可能为开发更有效的干预措施而介绍,以增强口头
该组的健康结果,从而阻止了AD或ARD的发展或消除。
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)

暂无数据
数据更新时间:2024-06-01
Fritzie Arce-McSh...的其他基金
The neural basis of touch and proprioreception in the primate orofacial sensorimotor cortex
灵长类口面部感觉运动皮层触觉和本体感受的神经基础
- 批准号:1054365610543656
- 财政年份:2021
- 资助金额:$ 138.89万$ 138.89万
- 项目类别:
The neural basis of touch and proprioreception in the primate orofacial sensorimotor cortex
灵长类口面部感觉运动皮层触觉和本体感受的神经基础
- 批准号:1035978810359788
- 财政年份:2021
- 资助金额:$ 138.89万$ 138.89万
- 项目类别:
Disambiguating natural aging from Alzheimer's disease through changes in oral neuromechanics
通过改变口腔神经力学来消除自然衰老与阿尔茨海默病的关系
- 批准号:1025679510256795
- 财政年份:2020
- 资助金额:$ 138.89万$ 138.89万
- 项目类别:
Disambiguating natural aging from Alzheimer's disease through changes in oral neuromechanics
通过改变口腔神经力学来消除自然衰老与阿尔茨海默病的关系
- 批准号:1054323710543237
- 财政年份:2020
- 资助金额:$ 138.89万$ 138.89万
- 项目类别:
Disambiguating natural aging from Alzheimer's disease through changes in oral neuromechanics
通过改变口腔神经力学来消除自然衰老与阿尔茨海默病的关系
- 批准号:1005561910055619
- 财政年份:2020
- 资助金额:$ 138.89万$ 138.89万
- 项目类别:
The neural basis of touch and proprioception in the primate orofacial sensorimotor cortex
灵长类口面部感觉运动皮层触觉和本体感觉的神经基础
- 批准号:98957229895722
- 财政年份:2018
- 资助金额:$ 138.89万$ 138.89万
- 项目类别:
相似国自然基金
来源和老化过程对大气棕碳光吸收特性及环境气候效应影响的模型研究
- 批准号:42377093
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
内源DOM介导下微塑料的老化过程及对植物的影响机制
- 批准号:42377233
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
老化过程对沙尘辐射效应和反馈机制的影响研究
- 批准号:42375107
- 批准年份:2023
- 资助金额:50.00 万元
- 项目类别:面上项目
生物炭原位修复底泥PAHs的老化特征与影响机制
- 批准号:42307107
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
河口潮滩中轮胎磨损颗粒的光老化特征及对沉积物氮素转化的影响与机制
- 批准号:42307479
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
相似海外基金
Fluency from Flesh to Filament: Collation, Representation, and Analysis of Multi-Scale Neuroimaging data to Characterize and Diagnose Alzheimer's Disease
从肉体到细丝的流畅性:多尺度神经影像数据的整理、表示和分析,以表征和诊断阿尔茨海默病
- 批准号:1046225710462257
- 财政年份:2023
- 资助金额:$ 138.89万$ 138.89万
- 项目类别:
Project 3: 3-D Molecular Atlas of cerebral amyloid angiopathy in the aging brain with and without co-pathology
项目 3:有或没有共同病理的衰老大脑中脑淀粉样血管病的 3-D 分子图谱
- 批准号:1055589910555899
- 财政年份:2023
- 资助金额:$ 138.89万$ 138.89万
- 项目类别:
Impact of Mitochondrial Lipidomic Dynamics and its Interaction with APOE Isoforms on Brain Aging and Alzheimers Disease
线粒体脂质组动力学及其与 APOE 亚型的相互作用对脑衰老和阿尔茨海默病的影响
- 批准号:1064561010645610
- 财政年份:2023
- 资助金额:$ 138.89万$ 138.89万
- 项目类别:
Reversal of Age-Associated Damage in the Planarian Germline
涡虫种系中年龄相关损伤的逆转
- 批准号:1060623410606234
- 财政年份:2023
- 资助金额:$ 138.89万$ 138.89万
- 项目类别:
Heart-brain MRI for the evaluation of hemodynamic coupling in aging and Alzheimer's disease
心脑 MRI 用于评估衰老和阿尔茨海默氏病的血流动力学耦合
- 批准号:1057141110571411
- 财政年份:2023
- 资助金额:$ 138.89万$ 138.89万
- 项目类别: