Diversity Supplement (Qudrat Abdulwahab) for Role of pericyte nanotubes in age-related neurovascular dysfunction

周细胞纳米管在年龄相关神经血管功能障碍中的作用的多样性补充剂(Qudrat Abdulwahab)

基本信息

  • 批准号:
    10702114
  • 负责人:
  • 金额:
    $ 11.96万
  • 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:
    2022-05-15 至 2024-04-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Alzheimer’s disease and Alzheimer’s disease associated dementias are characterized by marked alterations in neural function and associated cognitive decline. Though changes to neurons themselves are important, recent findings by our group and others suggest another major contributor to pathogenesis: alterations to neurovascular coupling. In Alzheimer’s disease, signaling between neurons and vessels appears to break down, accompanied by defects in vessel responses, cerebral amyloid angiopathy, and structural vascular alterations. However, little is known about the cellular or molecular basis of these changes. In this proposal, we identify a key mechanism responsible for maintaining vessel integrity in the context of aging and Alzheimer’s using the superbly tractable murine retina. We have shown that different retina neuron types exhibit distinct age- and Alzheimer’s disease-related dystrophies, and that dopaminergic neurons are a central target. In parallel, our data now reveal that neural changes are accompanied by distinct vascular dystrophies, with particular disruption to pericytes and their novel nanotube-like processes. Further, using genetic and pharmacological methods we and others have shown that dopamine can directly influence vascular organization and function and signal to pericytes. These data suggest that Alzheimer’s disease alters neuro- vascular coupling via declines in dopamine driven pericyte structure and function. In Aim 1, we determine how Alzheimer’s disease regulates vasculature structure and function, with a particular focus on pericytes. We test the hypothesis that pericyte alterations are accompanied by functional declines in vascular hemodynamics, loss of coupling nanotubes, and locally associated neural decline. In Aim 2, we examine the neural signaling defects causal to vascular structure and functional declines. Our preliminary data suggest that dopaminergic neurons are reduced in Alzheimer’s disease, and that dopamine is required for maintaining vessel integrity. We thus test the idea that declines in dopamine signaling are causal to vasculature dysfunction in Alzheimer’s disease and can be targeted to mitigate vascular pathology. These studies will lead to the identification of molecular pathways that drive neurovascular dysfunction in Alzheimer’s disease that may ultimately be useful for preventing pathogenesis.
项目总结

项目成果

期刊论文数量(0)
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Melanie A Samuel其他文献

West Nile Virus from Infected Neurons T Cells Require Perforin to Clear + Cd8
来自受感染神经元的西尼罗河病毒 T 细胞需要穿孔素来清除 Cd8
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Diamond Bimmi Shrestha;Melanie A Samuel;Michael S
  • 通讯作者:
    Michael S

Melanie A Samuel的其他文献

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{{ truncateString('Melanie A Samuel', 18)}}的其他基金

Microglial plasticity mechanisms in the developing retina
视网膜发育中的小胶质细胞可塑性机制
  • 批准号:
    10716629
  • 财政年份:
    2023
  • 资助金额:
    $ 11.96万
  • 项目类别:
Dopamine Mediated Control of Retinal Vascular Integrity
多巴胺介导的视网膜血管完整性控制
  • 批准号:
    10705700
  • 财政年份:
    2022
  • 资助金额:
    $ 11.96万
  • 项目类别:
Role of perictyte nanotubes in age-related neurovascular dysfunction
周细胞纳米管在年龄相关神经血管功能障碍中的作用
  • 批准号:
    10452103
  • 财政年份:
    2022
  • 资助金额:
    $ 11.96万
  • 项目类别:
Molecular Basis of Outer Retina Development and Repair
外视网膜发育和修复的分子基础
  • 批准号:
    10269817
  • 财政年份:
    2020
  • 资助金额:
    $ 11.96万
  • 项目类别:
Molecular Basis of Outer Retina Development and Repair
外视网膜发育和修复的分子基础
  • 批准号:
    10652910
  • 财政年份:
    2019
  • 资助金额:
    $ 11.96万
  • 项目类别:
Molecular Basis of Outer Retina Development and Repair
外视网膜发育和修复的分子基础
  • 批准号:
    10652031
  • 财政年份:
    2019
  • 资助金额:
    $ 11.96万
  • 项目类别:
Diversity Supplement (Pilar Andrade) for Molecular Basis of Outer Retina Development and Repair
外视网膜发育和修复的分子基础的多样性补充剂(Pilar Andrade)
  • 批准号:
    10428900
  • 财政年份:
    2019
  • 资助金额:
    $ 11.96万
  • 项目类别:
Molecular Basis of Outer Retina Development and Repair
外视网膜发育和修复的分子基础
  • 批准号:
    10453570
  • 财政年份:
    2019
  • 资助金额:
    $ 11.96万
  • 项目类别:
Molecular Basis of Outer Retina Development and Repair
外视网膜发育和修复的分子基础
  • 批准号:
    10653950
  • 财政年份:
    2019
  • 资助金额:
    $ 11.96万
  • 项目类别:
Molecular Basis of Outer Retina Development and Repair
外视网膜发育和修复的分子基础
  • 批准号:
    10206150
  • 财政年份:
    2019
  • 资助金额:
    $ 11.96万
  • 项目类别:

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