Behavioral and physiological measurements of hearing in mouse models of Alzheimer's Disease
阿尔茨海默病小鼠模型听力的行为和生理测量
基本信息
- 批准号:10878437
- 负责人:
- 金额:$ 16.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-04-01 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AcousticsAffectAlzheimer&aposs disease modelAlzheimer&aposs disease related dementiaAnimal ModelAnxietyAreaAttentionAuditory Brainstem ResponsesAuditory systemBehavioralBiologicalBlood VesselsBrainBrain PathologyCentral Nervous SystemCharacteristicsCognitionCognitiveCognitive deficitsDNA Sequence AlterationDataData SetDementiaEmotionalFemaleFrightFunctional disorderFundingFutureGene Expression RegulationGene MutationGenesGeneticGenotypeGoalsHearingHumanHuman BioMolecular Atlas ProgramImpaired cognitionIndividualInvestigationKnockout MiceKnowledgeLinkMetabolic dysfunctionMetabolismModalityModelingMusNerve DegenerationNeuronsPathologicPeripheralPeripheral Nervous SystemPersonsPhenotypePhysiologicalPhysiologyPrevalenceResearchSensoryStartle ReactionStressVisualWorkbehavioral phenotypingdata repositoryepidemiology studygenetic risk factorhearing impairmenthearing loss treatmenthearing measurementhuman tissueinterestmalemouse modelneuralnovel therapeutic interventionparent grantpreclinical studypreventprogramssexsoundtargeted treatment
项目摘要
Project Summary
A link between hearing loss and dementia is well established from epidemiological studies; however, whether or
not there is a causal link between hearing loss and dementia is unclear. The primary goal of the proposed
research is to use Common Fund datasets to investigate common genetic mutations associated with hearing
dysfunction and cognitive deficits. The proposed research extends the scope of the parent grant which focuses
on characterizing the behavioral and physiological trajectory of hearing loss in three specific mouse models with
gene mutations that result in brain pathologies mimicking certain aspects of Alzheimer’s and related dementias
(ADRD) in humans. While these models are useful for investigating the potential contribution of specific
predetermined pathological trajectories in hearing dysfunction, they do not adequately recapitulate human
dementias, which may arise from a host of mechanisms and display varying cognitive-behavioral phenotypes.
Identification of genetic factors that predispose a person to both hearing dysfunction and dementia is critical for
developing more valid animal models and probing potential mechanisms to target with biomedical treatments.
We hypothesize that abnormal cognition will be more prevalent in KO mice with hearing dysfunction compared
to those without hearing dysfunction. Our research will address this knowledge gap through two Specific Aims
that use Common Fund data to investigate additional genotype-phenotype relationships between hearing
dysfunction and cognitive deficits: 1) Analyze correlations between hearing phenotypes and cognitive-emotional
behavioral phenotypes in data from the Knockout Mouse Phenotyping Program (KOMP2) to identify common
genetic mechanisms, and 2) Compare genes of interest identified in Aim 1 against publicly available data in the
Human BioMolecular Atlas Program (HuBMAP) and other publicly available data repositories to determine which
human tissues express these genes and which genes are known to be expressed in the peripheral and central
auditory systems. Additionally, we will quantify the co-occurrence of hearing dysfunction, cognitive deficits, and
anxiety, fear, or stress phenotypes. We will consider sex as a biological variable to determine if hearing
dysfunction with cognitive phenotypes are more prevalent in males or females in the KOMP2 dataset. This work
will inform future investigations linking the trajectory of hearing dysfunction with cognitive deficits, including
ADRD, and provide potential targets for future preclinical studies investigating novel therapeutic interventions.
项目摘要
流行病学研究很好地确定了听力损失和痴呆症之间的联系;然而,无论或
目前还不清楚听力损失和痴呆症之间是否存在因果关系。建议的主要目标是
这项研究将使用共同基金的数据集来调查与听力相关的常见基因突变
功能障碍和认知缺陷。拟议的研究扩大了家长资助的范围,重点是
三种特定的小鼠听力损失模型的行为和生理轨迹特征
导致类似阿尔茨海默氏症和相关痴呆某些方面的脑部病理的基因突变
(ADRD)在人类身上。虽然这些模型对于研究特定的
听力障碍的预定病理轨迹,它们不能充分概括人类
痴呆症可能由多种机制引起,表现出不同的认知-行为表型。
识别易患听力障碍和痴呆症的遗传因素对
开发更有效的动物模型,探索以生物医学治疗为靶点的潜在机制。
我们假设,与听力障碍相比,认知异常在KO小鼠中更普遍
给那些没有听力障碍的人。我们的研究将通过两个具体目标来解决这一知识差距
使用共同基金的数据来调查听力之间的其他基因-表型关系
功能障碍与认知缺陷:1)分析听力表型与认知情绪的相关性
来自基因敲除小鼠表型程序(KOMP2)的数据中的行为表型以识别共同的
遗传机制,以及2)将目标1中确定的感兴趣基因与
人类生物分子图谱计划(HuBMAP)和其他公开可用的数据存储库,以确定
人类组织表达这些基因,已知哪些基因在外周和中央表达
听觉系统。此外,我们将量化听力障碍、认知障碍和
焦虑、恐惧或压力表型。我们将把性别作为一个生物变量来确定是否听力
在KOMP2数据集中,具有认知表型的功能障碍在男性或女性中更为普遍。这部作品
将为未来将听力障碍与认知障碍联系起来的研究提供信息,包括
ADRD,并为未来研究新的治疗干预措施的临床前研究提供潜在靶点。
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 }}
MICHEAL L DENT其他文献
MICHEAL L DENT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('MICHEAL L DENT', 18)}}的其他基金
Behavioral and physiological measurements of hearing in mouse models of Alzheimer's Disease
阿尔茨海默病小鼠模型听力的行为和生理测量
- 批准号:
10647340 - 财政年份:2023
- 资助金额:
$ 16.94万 - 项目类别:
Age differences in perceptual consequences of noise exposure
噪声暴露感知后果的年龄差异
- 批准号:
10392912 - 财政年份:2018
- 资助金额:
$ 16.94万 - 项目类别:
Supplement for temporal bone tissue scanning equipment
颞骨组织扫描设备的补充
- 批准号:
10449921 - 财政年份:2018
- 资助金额:
$ 16.94万 - 项目类别:
Age-related hearing deficits in noise-exposed mouse models of Alzheimer's Disease
暴露于噪音的阿尔茨海默病小鼠模型中与年龄相关的听力缺陷
- 批准号:
10284502 - 财政年份:2018
- 资助金额:
$ 16.94万 - 项目类别:
Age differences in perceptual consequences of noise exposure
噪声暴露感知后果的年龄差异
- 批准号:
9914000 - 财政年份:2018
- 资助金额:
$ 16.94万 - 项目类别:
相似海外基金
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 16.94万 - 项目类别:
Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 16.94万 - 项目类别:
Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 16.94万 - 项目类别:
Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 16.94万 - 项目类别:
Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 16.94万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 16.94万 - 项目类别:
Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 16.94万 - 项目类别:
Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 16.94万 - 项目类别:
Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
- 批准号:
23K00129 - 财政年份:2023
- 资助金额:
$ 16.94万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
- 批准号:
2883985 - 财政年份:2023
- 资助金额:
$ 16.94万 - 项目类别:
Studentship