Department of Physiology and Pharmacology, Laboratory of Experimental Audiology, Karolinska Institutet, Solanvägen 9, 17177 Stockholm Sweden.
Department of Physiology and Pharmacology, Laboratory of Experimental Audiology, Karolinska Institutet, Solanvägen 9, 17177 Stockholm Sweden.
Hear Res. 2022 Mar 1;415:108395. doi: 10.1016/j.heares.2021.108395. Epub 2021 Nov 15.
Noise trauma involves a plethora of mechanisms including reactive oxygen species, apoptosis, tissue damage, and inflammation. Recently, circadian mechanisms were also found to contribute to the vulnerability to noise trauma in mice, with greater damage occurring during their active phase (nighttime), when compared to similar noise exposures during their inactive phase (daytime). These effects seem to be regulated by mechanisms involving Bdnf responses to noise trauma and circulating levels of corticosterone (CORT). However, recent studies using different noise paradigms show contradicting results and it remains unclear how universal these findings are. Here we show that these findings differ even between substrains of mice and are restricted to a narrow window of noise intensity. We found that CBA/Sca mice exposed to 103 dB SPL display differential day/night noise sensitivity as measured by auditory brainstem responses (ABRs), but not at 100 (where full recovery is observed in day or night exposed mice) or 105 dB SPL (where permanent damage is found in both groups). In contrast, neither CBA/CaJ or CBA/JRj displayed such differences in day/night noise sensitivity, whatever noise intensity used. These effects appeared to be independent from outer hair cell function, as distortion product otoacoustic emissions appeared equally affected by day or night noise exposure, in all strains and in all noise conditions. Minor differences in ribbon counts or synaptic pairing were found in CBA/Sca mice, which were inconsistent with ABR wave 1 amplitude changes. Interestingly, CORT levels peaked in CBA/Sca mice at the onset of darkness at zeitgeber time 12 reaching levels of 43.8 ng/ml, while in the CBA/CaJ and the CBA/JRj, levels were 11.9 and 15.6 ng/ml respectively and peaking 4 h earlier (zeitgeber time 8). These findings were consistent with higher period of daily rhythm in CBA/Sca mice when measured in complete darkness using running wheels (23.7 h), than in CBA/CaJ (23.45 h) or CBA/JRj (23.13 h). In conclusion, our study suggests that the differential vulnerability to noise trauma between inactive and active phase is not universal and is as sensitive as substrain differences that might be governed by the circadian amplitude of the circulating CORT profiles.
噪声性听力损伤涉及多种机制，包括活性氧物种、细胞凋亡、组织损伤和炎症。最近，昼夜节律机制也被发现有助于小鼠对噪声性听力损伤的易感性，与在非活动期（白天）进行类似的噪声暴露相比，在活动期（夜间）发生的损伤更大。这些影响似乎受到涉及噪声性听力损伤时 Bdnf 反应和皮质酮（CORT）循环水平的机制的调节。然而，最近使用不同噪声范式的研究显示出相互矛盾的结果，并且尚不清楚这些发现的普遍性如何。在这里，我们表明，这些发现即使在小鼠的亚系之间也存在差异，并且仅限于噪声强度的狭窄窗口。我们发现，暴露于 103 dB SPL 的 CBA/Sca 小鼠的听觉脑干反应（ABR）显示出不同的日/夜噪声敏感性，但在 100 dB SPL（在白天或夜间暴露的小鼠中观察到完全恢复）或 105 dB SPL（两组均发现永久性损伤）则不然。相比之下，无论使用何种噪声强度，CBA/CaJ 或 CBA/JRj 均未显示出日/夜噪声敏感性的差异。这些影响似乎与外毛细胞功能无关，因为畸变产物耳声发射似乎同样受到白天或夜间噪声暴露的影响，在所有品系和所有噪声条件下都是如此。在 CBA/Sca 小鼠中发现了微小的带状计数或突触配对差异，但与 ABR 波 1 幅度变化不一致。有趣的是，在 CBA/Sca 小鼠中，CORT 水平在 Zeitgeber 时间 12 时黑暗开始时达到峰值，为 43.8ng/ml，而在 CBA/CaJ 和 CBA/JRj 中，水平分别为 11.9 和 15.6ng/ml，峰值提前 4 小时（Zeitgeber 时间 8）。这些发现与在使用跑步轮在完全黑暗中测量时 CBA/Sca 小鼠的每日节律周期较长（23.7 小时）一致，而与 CBA/CaJ（23.45 小时）或 CBA/JRj（23.13 小时）相比。总之，我们的研究表明，在不活动期和活动期之间对噪声性听力损伤的易感性差异并非普遍存在，并且与昼夜节律振幅的亚系差异一样敏感，昼夜节律振幅可能受循环 CORT 谱的调节。
