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：
10647340
负责人：
MICHEAL L DENT
金额：
$ 17.72万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
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：
https://reporter.nih.gov/project-details/10647340
关键词：
3xTg-AD mouse APP-PS1 Acceleration Active Listening Affect Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer&apos s disease patient Alzheimer&apos s disease related dementia Anesthesia procedures Animal Model Animals Audiology Auditory Auditory Brainstem Responses Auditory Evoked Potentials Auditory system Behavior Behavioral Biological Assay Brain Pathology Brain Stem Chronic Clinical Research Cochlea Communication Compensation Environment Epidemiology Evoked Potentials Exposure to Female Functional disorder Goals Hair Cells Health Hearing Hearing Tests Human Impairment Laboratories Learning Link Longevity Measurement Measures Mediating Methods Modeling Mouse Strains Mus Mutation Nature Neurofibrillary Tangles Noise Operant Conditioning Organism Pathologic Pathology Patients Performance Peripheral Persons Phenotype Physiological Positive Reinforcements Process Psychoacoustics Reporting Research Research Personnel Response Latencies Role Severities Stimulus Structure Techniques Testing Time Training age effect auditory processing awake base behavior measurement cognitive function effectiveness testing epidemiology study experience experimental study healthy aging hearing impairment hearing measurement hearing screening improved male mouse model neuropathology selective attention sex sound

3xTg-AD mouse APP-PS1 Acceleration Active Listening Affect Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer&apos s disease patient Alzheimer&apos s disease related dementia Anesthesia procedures Animal Model Animals Audiology Auditory Auditory Brainstem Responses Auditory Evoked Potentials Auditory system Behavior Behavioral Biological Assay Brain Pathology Brain Stem Chronic Clinical Research Cochlea Communication Compensation Environment Epidemiology Evoked Potentials Exposure to Female Functional disorder Goals Hair Cells Health Hearing Hearing Tests Human Impairment Laboratories Learning Link Longevity Measurement Measures Mediating Methods Modeling Mouse Strains Mus Mutation Nature Neurofibrillary Tangles Noise Operant Conditioning Organism Pathologic Pathology Patients Performance Peripheral Persons Phenotype Physiological Positive Reinforcements Process Psychoacoustics Reporting Research Research Personnel Response Latencies Role Severities Stimulus Structure Techniques Testing Time Training age effect auditory processing awake base behavior measurement cognitive function effectiveness testing epidemiology study experience experimental study healthy aging hearing impairment hearing measurement hearing screening improved male mouse model neuropathology selective attention sex sound

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项目摘要

Project Summary Although Alzheimer’s disease and related dementias (ADRD) and hearing loss often co-occur, the nature of this relationship is still largely unknown. Many mouse models have been developed to better understand the physiological and behavioral effects of specific ADRD-related brain pathologies, but the research on hearing in these mice lags human studies and has not produced definitive results, with huge variability across laboratories. One study suggested that exposure to damaging noise may exacerbate the ADRD pathology in one ADRD model mouse strain, but other labs have not found similar effects in other mouse strains. Further, most researchers pursuing information about hearing, hearing loss, and aging in mouse models of ADRD utilize physiological methods in anesthetized mice or reflexive methods to assess hearing status. While these techniques are informative, neither method accurately portrays how an awake, behaving organism perceives the world around them. This is critical because epidemiological and audiological studies of humans with ADRD, as well as healthy-aging humans, rely primarily on behavioral measures of hearing dysfunction. For this reason, hearing in quiet and in noise at several time points in the mouse lifespan in three mouse models of ADRD using behavioral psychoacoustic assessments and physiological evoked potential techniques will be conducted. Comparisons of results from male and female mice trained with operant conditioning and positive reinforcement to those from anesthetized and unanesthetized mice using auditory brainstem response and middle latency response recordings will be made. Comparisons of behavioral results to physiological measurements will provide information about whether behavioral performance reflects central compensation processes and which physiological test conditions correspond to behavioral deficits. These experiments will help to better appreciate how aging, sex, and noise affect communication in mice, possibly leading to advances in understanding communication issues in human patients suffering from ADRD.

项目摘要尽管阿尔茨海默氏病和相关痴呆症（ADRD）和听力损失通常同时发生，但这种关系仍然很大程度上是未知的。已经开发了许多鼠标模型来更好地了解特定ADRD相关的脑病理学的生理和行为影响，但是听力研究在这些小鼠中，人类研究滞后，尚未产生明确的结果，在整个实验室。一项研究表明，暴露于损坏的噪声可能会加剧ADRD病理在一种ADRD模型的小鼠菌株中，但其他实验室在其他小鼠菌株中没有发现相似的效果。此外，大多数研究人员在鼠标模型中寻求有关听力，听力损失和衰老的信息 ADRD在麻醉小鼠或反射方法中利用物理方法来评估听力状态。尽管这些技术是有益的，但两种方法都没有准确地描绘出醒着的方式有机体感知到周围的世界。这很关键，因为流行病学和听力学研究具有ADRD的人类以及健康衰老的人类，主要依靠听力的行为度量功能障碍。因此，在鼠标寿命中的几个时间点中听到安静和噪音的声音使用行为心理声学评估和生理诱发的三种ADRD的小鼠模型潜在技术将进行。比较接受训练的雄性和雌性小鼠的结果使用麻醉和未经麻醉的小鼠进行操作调节和阳性加强听觉的脑干响应和中潜伏期响应记录将进行。比较物理测量的行为结果将提供有关行为是否的信息绩效反映了中央补偿过程，哪些物理测试条件对应于行为定义。这些实验将有助于更好地理解衰老，性别和噪音如何影响小鼠的交流，可能导致理解人类交流问题的进步患有ADRD的患者。