ACOUSTIC ENVIRONMENT EFFECTS ON DPOAES IN AGING MICE

最近对年龄相关性听力损失小鼠的研究表明，通过听觉脑干反应（ABRs）和螺旋神经节细胞计数测量，每天12小时由中等水平脉冲噪声爆发组成的增强声环境（AAE）可以显著延缓与这种基于基因的加速衰老过程相关的功能和组织学变化。这些改善的影响是否也破坏了感觉受体细胞的相关变性尚未确定。该研究的主要目的是评估AAE在多大程度上（如果有的话）影响表现为快速发作性老年性痴呆的小鼠的进行性感觉细胞丧失。这一目标将通过功能和组织学方法在两种小鼠中完成，包括过早老化的C57s和正常的cba，分别通过监测反映外毛细胞（ohc）正常微力学活动的扭曲产物耳声发射（dpoae），并评估毛细胞在塑料嵌入的整个耳蜗支架中的存在。C57菌株在6个月大时表现出进行性感觉细胞退化，而CBA菌株在18个月大时表现出正常的耳蜗功能和感觉细胞存在。计划中的实验将确定暴露于AAE的实验组C57的dpoae和耳蜗组织病理学是否与在正常体内条件下饲养的对照C57的相同测量结果不同。AAE治疗的结果也将与相似组的CBA小鼠进行比较，CBA小鼠由于暴露在相同的声学富集环境或体内条件下，预计不会出现任何变化。还将获得abr，以便将这些发现与早期结果进行比较，并确定在没有显著的aae诱导的耳蜗效应的情况下它们是否有所改善。AAE可以保持OHC功能，防止或延缓毛细胞变性，这一发现将对听觉感觉受体的可塑性产生深远的影响，并表明某些遗传形式的听力损失的不利影响可以被有意地逆转。

Recent research in mice with age-related hearing loss has established that an augmented acoustic environment (AAE) consisting of moderate-level pulsed noise bursts presented for 12 hrs per day can, as measured by auditory brainstem responses (ABRs) and spiral ganglion-cell counts, dramatically retard the functional and histological changes typically associated with such genetically-based accelerated aging processes. Whether these ameliorating influences also disrupt the associated degeneration of sensory receptor cells has not yet been determined. The primary goal of the proposed study is to assess to what extent, if any, an AAE affects the progressive sensory-cell loss in mice that exhibit rapid-onset presbycusis. This aim will be accomplished using functional and histological methods in two strains of mice, consisting of the prematurely aging C57s and the normal CBAs, by, respectively, monitoring distortion-product otoacoustic emissions (DPOAEs) that reflect the normal micromechanical activity of outer hair cells (OHCs), and evaluating hair-cell presence in plastic-embedded whole mounts of the cochlea. The C57 strain shows progressive sensory-cell degeneration that is advanced by age 6 mo, whereas the CBA strain exhibits normal cochlear function and sensory-cell presence up to age 18 mo. The planned experiments will determine if DPOAEs and cochlear histopathology in the C57s differ in an experimental group exposed to an AAE as compared to the identical measures obtained for control C57s housed under normal vivarium conditions. The outcome of the AAE treatment will also be compared to similar groups of CBA mice, which are not expected to show any changes as a result of exposure to the same acoustically enriched environment or vivarium conditions. ABRs will also be obtained in order to facilitate comparisons of these findings to the earlier results as well as to determine if they improve in the absence of significant AAE-induced cochlear effects. The finding that an AAE can preserve OHC function and prevent or retard hair-cell degeneration would have far-reaching implications for plasticity of auditory sensory receptors, and indicate that the adverse effects of certain genetic forms of hearing loss can be deliberately reversed.