Jensen Jane Bjerg, Lysaght Andrew C, Liberman M Charles, Qvortrup Klaus, Stankovic Konstantina M
Eaton-Peabody Laboratories and Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA, 02114, United States of America; Department of Otology and Laryngology, Harvard Medical School, Boston, MA, 02115, United States of America; Department of Biomedical Sciences, CFIM, University of Copenhagen, 2200, Copenhagen N, Denmark.
Eaton-Peabody Laboratories and Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA, 02114, United States of America; Department of Otology and Laryngology, Harvard Medical School, Boston, MA, 02115, United States of America; Program in Speech and Hearing Bioscience and Technology, Division of Health Science and Technology, Harvard and Massachusetts Institute of Technology, Boston, MA, 02139, United States of America.
PLoS One. 2015 May 8;10(5):e0125160. doi: 10.1371/journal.pone.0125160. eCollection 2015.
Moderate acoustic overexposure in adult rodents is known to cause acute loss of synapses on sensory inner hair cells (IHCs) and delayed degeneration of the auditory nerve, despite the completely reversible temporary threshold shift (TTS) and morphologically intact hair cells. Our objective was to determine whether a cochlear synaptopathy followed by neuropathy occurs after noise exposure in pubescence, and to define neuropathic versus non-neuropathic noise levels for pubescent mice. While exposing 6 week old CBA/CaJ mice to 8-16 kHz bandpass noise for 2 hrs, we defined 97 dB sound pressure level (SPL) as the threshold for this particular type of neuropathic exposure associated with TTS, and 94 dB SPL as the highest non-neuropathic noise level associated with TTS. Exposure to 100 dB SPL caused permanent threshold shift although exposure of 16 week old mice to the same noise is reported to cause only TTS. Amplitude of wave I of the auditory brainstem response, which reflects the summed activity of the cochlear nerve, was complemented by synaptic ribbon counts in IHCs using confocal microscopy, and by stereological counts of peripheral axons and cell bodies of the cochlear nerve from 24 hours to 16 months post exposure. Mice exposed to neuropathic noise demonstrated immediate cochlear synaptopathy by 24 hours post exposure, and delayed neurodegeneration characterized by axonal retraction at 8 months, and spiral ganglion cell loss at 8-16 months post exposure. Although the damage was initially limited to the cochlear base, it progressed to also involve the cochlear apex by 8 months post exposure. Our data demonstrate a fine line between neuropathic and non-neuropathic noise levels associated with TTS in the pubescent cochlea.
已知成年啮齿动物受到中度听觉过度暴露会导致感觉性内毛细胞（IHC）上的突触急性丧失以及听神经的延迟退化，尽管暂时阈移（TTS）完全可逆且毛细胞形态完整。我们的目标是确定青春期噪声暴露后是否会发生耳蜗突触病变继而引发神经病变，并确定青春期小鼠的神经病变性与非神经病变性噪声水平。在将6周龄的CBA/CaJ小鼠暴露于8 - 16 kHz带通噪声2小时的过程中，我们将97分贝声压级（SPL）定义为与TTS相关的这种特定类型神经病变性暴露的阈值，将94分贝SPL定义为与TTS相关的最高非神经病变性噪声水平。暴露于100分贝SPL会导致永久性阈移，尽管据报道16周龄小鼠暴露于相同噪声仅会引起TTS。听觉脑干反应的I波振幅反映了耳蜗神经的总和活动，通过共聚焦显微镜对IHC中的突触带计数以及在暴露后24小时至16个月对耳蜗神经外周轴突和细胞体进行体视学计数来补充。暴露于神经病变性噪声的小鼠在暴露后24小时即表现出即刻的耳蜗突触病变，并在暴露后8个月出现以轴突回缩为特征的延迟性神经退行性变，在暴露后8 - 16个月出现螺旋神经节细胞丢失。尽管损伤最初局限于耳蜗底部，但在暴露后8个月时也发展到累及耳蜗顶部。我们的数据表明，青春期耳蜗中与TTS相关的神经病变性和非神经病变性噪声水平之间存在细微差别。
