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

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.

项目概要尽管阿尔茨海默病及相关痴呆症 (ADRD) 和听力损失经常同时发生，但其本质这种关系在很大程度上仍然未知。为了更好地理解这种关系，人们已经开发了许多小鼠模型。特定 ADRD 相关脑部病理的生理和行为影响，但对听力的研究在这些小鼠中进行的研究滞后于人类研究，并且尚未产生明确的结果，并且各研究之间存在巨大差异一项研究表明，暴露于破坏性噪音可能会使 ADRD 病理恶化。在一种 ADRD 模型小鼠品系中存在这种效应，但其他实验室尚未在其他小鼠品系中发现类似的效果。此外，大多数研究人员在小鼠模型中寻找有关听力、听力损失和衰老的信息 ADRD 利用麻醉小鼠的生理方法或反射方法来评估听力状态。虽然这些技术提供了丰富的信息，但两种方法都无法准确地描述清醒的、行为的这对于生物体感知周围的世界至关重要，因为流行病学和听力学研究。患有 ADRD 的人和健康老龄化的人主要依赖于听力行为测量由于这个原因，小鼠寿命中的几个时间点在安静和噪音中都出现听力障碍。使用行为心理声学评估和生理诱发的三种 ADRD 小鼠模型将比较受过训练的雄性和雌性小鼠的结果。使用以下方法对麻醉和未麻醉小鼠进行操作性条件反射和正向强化将进行听觉脑干反应和中潜伏期反应记录的比较。行为结果与生理测量将提供有关行为是否性能中心补偿过程以及对应的生理测试条件这些实验将有助于更好地了解衰老、性别和噪音的影响。小鼠的交流可能会促进理解人类交流问题的进展患有 ADRD 的患者。