Hearing loss is an early biomarker in APP/PS1 Alzheimer's disease mice
Hearing loss is an early biomarker in APP/PS1 Alzheimer's disease mice
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DOI：
10.1016/j.neulet.2019.134705
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发表时间：
2020-01-19
影响因子：
2.5
通讯作者：
Zhao, Hong-Bo
中科院分区：
文献类型：
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作者：
Liu, Yang;Fang, Shu;Zhao, Hong-Bo
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是记忆力逐渐丧失和认知能力下降。在过去的十年里，人们发现感觉系统的缺陷可能与阿尔茨海默病高度相关。听觉是一种重要的神经感觉。然而，人们对AD患者的听力功能变化知之甚少。本研究使用APP/PS1 AD小鼠（Jackson Lab: Stack No. 004462）。通过听觉脑干反应（ABR）、畸变产物耳声发射（DPOAE）和耳蜗麦克风（CM）记录评估听力功能。野生型（WT）幼崽作为对照。我们发现以ABR阈值测量的APP/PS1 AD小鼠存在听力损失。听力损失早在2个月大时就出现了高频率，在该AD小鼠模型中，在6-7个月大时出现了空间学习缺陷。听力损失是进行性的，由高频向低频扩展。在3-4个月大时，全频范围内出现听力损失。此外，超阈ABR的IV和V波被消除，表明上脑干的下丘、外侧小丘核和内侧膝状体存在实质性损伤。APP/PS1 AD小鼠DPOAE也降低。然而，APP/PS1小鼠的CM没有减少。这些数据表明，与年龄相关的听力损失不同，APP/PS1 AD小鼠具有早发性听力损失。这些数据也表明，听力功能检测可以为早期发现AD和定位病变提供一种简单、灵敏、无创的筛查工具。
Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive loss of memory and cognitive decline. Over the last decade, it has been found that defects in sensory systems could be highly associated with AD. Hearing is an important neural sense. However, little is known about hearing functional changes in AD. In this study, APP/PS1 AD mice (Jackson Lab: Stack No. 004462) were used. Hearing function was assessed by auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE), and cochlear microphonics (CM) recordings. Wild-type (WT) littermates served as control. We found that APP/PS1 AD mice measured as ABR threshold had hearing loss. The hearing loss appeared at high frequency as early as 2 months old, prior to the reported occurrence of spatial learning deficit at 6-7 months of age in this AD mouse model. The hearing loss was progressive and extended from high frequency to low frequency. At 3-4 months old, the hearing loss appeared in the whole-frequency range. Moreover, the wave IV and V in the super-threshold ABR were eliminated, indicating substantial impairment in inferior colliculus, nuclei of lateral lemniscus, and medial geniculate body in the upper brainstem. DPOAE in APP/PS1 AD mice was also reduced. However, there was no reduction in CM in APP/PS1 mice. These data demonstrate that unlike age-related hearing loss APP/PS1 AD mice have early onset of hearing loss. These data also suggest that hearing function testing could provide a simple, sensitive, non-invasive screen-tool for early detecting AD and localizing lesion.