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随着年龄相关性耳蜗突触病导致的中枢听觉神经退行性变,间隙检测能力下降。

Gap detection ability declines with central auditory neurodegeneration following age-related cochlear synaptopathy.

机构信息

Department of Otolaryngology, Head and Neck Surgery, National Defense Medical College, Saitama, Japan.

出版信息

Eur J Neurosci. 2024 Oct;60(8):5861-5875. doi: 10.1111/ejn.16534. Epub 2024 Sep 5.

Abstract

Age-related hearing impairment (ARHI) is commonly associated with decreased auditory temporal resolution caused by auditory neurodegeneration. Age-related deterioration in gap detection ability, resulting in poor temporal auditory processing, is often attributed to pathophysiological changes in both the peripheral and central auditory systems. This study aimed to investigate whether the gap detection ability declines in the early stages of ageing and to determine its usefulness in detecting peripheral and central auditory degeneration. The study used 1-month-old (1 M), 6-month-old (6 M) and 12-month-old (12 M) mice to examine changes in gap detection ability and associated auditory pathophysiology. Although hearing thresholds did not significantly differ between the groups, the amplitude of auditory brainstem response (ABR) wave I decreased significantly in an age-dependent manner, consistent with age-related cochlear synaptopathy. The relative ABR amplitude ratio of waves 2 and 5 to wave 1 was significantly increased in 12 M mice, indicating that the central auditory system had increased in relative neuroactivity. A significant increase in gap detection thresholds was observed in 12 M mice compared to 1 M mice. Although cochlear synaptopathy and central hyperactivity were positively correlated with gap detection thresholds, central hyperactivity strongly influenced gap detection ability. In the cochlear nucleus and auditory cortex, the inhibitory synaptic expression of GAD65 and the expression of parvalbumin were significantly decreased in 12 M mice, consistent with central hyperactivity. Evaluating gap detection performance may allow the identification of decreased auditory temporal resolution in the early stages of ARHI, which is strongly associated with auditory neurodegeneration.

摘要

年龄相关性听力障碍(ARHI)通常与听觉神经退行性变引起的听觉时间分辨率下降有关。年龄相关性的缝隙检测能力下降,导致听觉时间处理能力差,这通常归因于外周和中枢听觉系统的病理生理变化。本研究旨在探讨缝隙检测能力是否在衰老的早期阶段下降,并确定其在检测外周和中枢听觉退行性变中的作用。该研究使用 1 个月(1M)、6 个月(6M)和 12 个月(12M)大的小鼠来研究缝隙检测能力的变化及其与相关听觉生理学的关系。尽管各组的听力阈值没有显著差异,但听觉脑干反应(ABR)波 I 的振幅随年龄呈依赖性显著降低,与年龄相关性耳蜗突触病一致。12M 小鼠的相对 ABR 波 2 和 5 与波 1 的振幅比显著增加,表明中枢听觉系统的相对神经活动增加。与 1M 小鼠相比,12M 小鼠的缝隙检测阈值显著增加。尽管耳蜗突触病和中枢过度活跃与缝隙检测阈值呈正相关,但中枢过度活跃对缝隙检测能力有很大影响。在耳蜗核和听觉皮层中,GAD65 的抑制性突触表达和 parvalbumin 的表达在 12M 小鼠中显著降低,与中枢过度活跃一致。评估缝隙检测性能可能有助于识别 ARHI 早期听觉时间分辨率的下降,这与听觉神经退行性变密切相关。

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