The role of Pou4f3 in age-related vestibular dysfunction
Pou4f3 在年龄相关前庭功能障碍中的作用
基本信息
- 批准号:10619025
- 负责人:
- 金额:$ 64.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-08-15 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:129 Mouse3xTg-AD mouseATAC-seqAdultAgeAge MonthsAgingAllelesAlzheimer&aposs disease modelAlzheimer&aposs disease related dementiaAnimalsAuditoryC57BL/6 MouseCell DeathCell SurvivalCellsCessation of lifeClassificationCochleaDNADataDevelopmental GeneDown-RegulationEarElderlyEmbryonic DevelopmentEpitheliumEquilibriumExhibitsFDA approvedFemaleFinancial costFoundationsFunctional disorderGenesGeneticGenomicsHair CellsHealthHealthcareHearingHumanImpaired cognitionInjectionsInner Hair CellsInvestigationLabyrinthLinkLocationModelingMotorMusMutationNervous System PhysiologyOrganPathologyPatternPhenotypePopulationPresbycusisPrevalencePrevention approachProcessPublic HealthQuality of lifeReflex actionRegulationRegulatory ElementRoleSensorimotor functionsSensorySensory HairSex DifferencesSynapsesSystemTamoxifenTask PerformancesTemporal bone structureTestingTimeTissuesVestibular Function TestsVestibular Hair Cellsage relatedagedcell agecognitive functioncognitive performancecostexperimental studyfallsgene therapygenetic deafnessimmunoreactivitymalemorris water mazemouse modelnoise exposurenovelobject recognitionoverexpressionpharmacologicpostnatalpreservationpreventprogressive hearing lossresponsetherapeutic targettranscription factor
项目摘要
Project Summary:
It has been estimated that more than 40% of older adults suffer vestibular (i.e. balance) deficits.
These losses cause numerous other problems associated with aging including cognitive decline
and injurious or fatal falls. There is also a strong link between age-related vestibular dysfunction
(ARVD) and Alzheimer's disease and related dementias. Despite the prevalence of these issues
and the massive toll they exert on public health and associated financial costs, the underlying
causes for ARVD are poorly understood. As a result, there are currently no FDA approved
therapies for ARVD. While a deep understanding of mechanistic causes is lacking, it has been
known for some time that a very common pathology that causes age related inner ear
dysfunction is the death of sensory cells called hair cells. Exactly why these cells die with age
remains a mystery. Here, we have identified a previously uncharacterized pattern in the
expression of the pro-survival gene, Pou4f3, where it is normally highly expressed in inner ear
hair cells, but is downregulated with age in a fashion that is correlated with hair cell death in the
balance organs of the inner ear. Furthermore, preliminary data suggest that deleting Pou4f3
causes detrimental phenotypes in vestibular hair cells, exacerbates hair cell death, and leads to
significant declines in vestibular function. We propose to build on these preliminary data by
further examining Pou4f3 changes in expression in vestibular organs with age and in models of
Alzheimer's disease. We will also more thoroughly characterize the effects of Pou4f3 deletion to
better understand the effects that deletion or hypomorhpism have on balance and neurological
functions. We also propose to examine genomic regulatory elements in inner ear tissues from
young and aged mice to identify causal mechanisms for Pou4f3 downregulation with age as well
as possibly discover other key genes involved in aging processes in the inner ear. Finally, we
will test whether overexpression of Pou4f3 can prevent sensory cell death and age related
vestibular declines. Our preliminary data suggest that Pou4f3 is a promising therapeutic target
for preserving balance function in the aging human population. The experiments proposed will
determine the validity of that overarching hypothesis and will provide a foundation from which to
launch several new investigations into Pou4f3-targeted pharmacological and gene therapy
approaches for the prevention of age related vestibular decline.
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)
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 }}
Brandon C. Cox其他文献
Generation of a <em>ChAT</em><sup><em>Cre</em></sup> mouse line without the early onset hearing loss typical of the C57BL/6J strain
- DOI:
10.1016/j.heares.2020.107896 - 发表时间:
2020-03-15 - 期刊:
- 影响因子:
- 作者:
Nichole L. Beebe;Colleen S. Sowick;Inga Kristaponyte;Alexander V. Galazyuk;Douglas E. Vetter;Brandon C. Cox;Brett R. Schofield - 通讯作者:
Brett R. Schofield
Hearing restoration through hair cell regeneration: A review of recent advancements and current limitations
通过毛细胞再生恢复听力:近期进展及当前局限综述
- DOI:
10.1016/j.heares.2025.109256 - 发表时间:
2025-06-01 - 期刊:
- 影响因子:2.500
- 作者:
Melissa M. McGovern;Brandon C. Cox - 通讯作者:
Brandon C. Cox
emSox2/em is required in supporting cells for normal levels of vestibular hair cell regeneration in adult mice
在成年小鼠的支持细胞中,emSox2/em 对于维持前庭毛细胞正常再生水平是必需的
- DOI:
10.1016/j.heares.2022.108642 - 发表时间:
2022-12-01 - 期刊:
- 影响因子:2.500
- 作者:
Amanda N. Ciani Berlingeri;Rémy Pujol;Brandon C. Cox;Jennifer S. Stone - 通讯作者:
Jennifer S. Stone
Brandon C. Cox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('Brandon C. Cox', 18)}}的其他基金
Consequences of chronic noise exposure in nonhuman primates
非人类灵长类动物长期暴露于噪音的后果
- 批准号:
10608454 - 财政年份:2022
- 资助金额:
$ 64.04万 - 项目类别:
The role of Pou4f3 in age-related vestibular dysfunction
Pou4f3 在年龄相关前庭功能障碍中的作用
- 批准号:
10468947 - 财政年份:2021
- 资助金额:
$ 64.04万 - 项目类别:
The role of Pou4f3 in age-related vestibular dysfunction
Pou4f3 在年龄相关前庭功能障碍中的作用
- 批准号:
10277134 - 财政年份:2021
- 资助金额:
$ 64.04万 - 项目类别:
p16INK4a in Cochlear Hair Cell Regeneration.
p16INK4a 在耳蜗毛细胞再生中的作用。
- 批准号:
7753757 - 财政年份:2009
- 资助金额:
$ 64.04万 - 项目类别:
p16INK4a in Cochlear Hair Cell Regeneration.
p16INK4a 在耳蜗毛细胞再生中的作用。
- 批准号:
8064638 - 财政年份:2009
- 资助金额:
$ 64.04万 - 项目类别:
p16INK4a in Cochlear Hair Cell Regeneration.
p16INK4a 在耳蜗毛细胞再生中的作用。
- 批准号:
8076759 - 财政年份:2009
- 资助金额:
$ 64.04万 - 项目类别:
相似海外基金
Novel PPAR-gamma agonist selectively activate the ligand binding domain of PPAR-gamma and improve pathology and memory deficits in a 3xTg-Ad mouse model.
新型 PPAR-gamma 激动剂选择性激活 PPAR-gamma 的配体结合域,改善 3xTg-Ad 小鼠模型的病理和记忆缺陷。
- 批准号:
8890576 - 财政年份:2015
- 资助金额:
$ 64.04万 - 项目类别:
Targeting Amyloid Beta Oligomers in the 3xTg-AD Mouse Model with scFv Antibodies
使用 scFv 抗体靶向 3xTg-AD 小鼠模型中的淀粉样蛋白 β 寡聚物
- 批准号:
7407908 - 财政年份:2008
- 资助金额:
$ 64.04万 - 项目类别: