Vázquez Ana E, Jimenez Ana M, Martin Glen K, Luebke Anne E, Lonsbury-Martin Brenda L
Department of Otolaryngology, Center for Neuroscience, University of California at Davis, 1515 Newton Court, Room 213, Davis, CA 95616, USA.
Hear Res. 2004 Aug;194(1-2):87-96. doi: 10.1016/j.heares.2004.03.017.
Cochlear function and susceptibility to noise over-exposure were examined in the congenic mouse strain B6.CAST+Ahl (B6.CAST) and compared to these same features in the CAST/Ei (CAST) and C57BL/6J (C57) parental strains. For both types of comparisons, the primary measure was the distortion-product otoacoustic emissions (DPOAE) at 2f1-2f2. Our assumption was that the B6.CAST mouse was corrected for the early onset age-related hearing loss (AHL) exhibited by one of its parental strains (C57) by the age-resistant properties of its other parental strain (CAST), and thus would exhibit neither AHL nor susceptibility to noise overstimulation effects. With respect to cochlear function, for 2.5-month mice, there was a tendency for DPOAEs to be slightly lower for mid-frequency primary tones for both C57 and B6.CAST mice, while the former mice showed clear AHL effects at the highest test frequency. However, by 5 months of age, the B6.CAST mice, like the CAST mice, displayed robust DPOAE levels that were significantly larger than DPOAE levels for the C57 mice, which were essentially absent for frequencies above about 30 kHz. To investigate the role of the Ahl gene in the susceptibility of the cochlea to the effects of noise over-exposure, two distinct paradigms consisting of temporary (TTS: 1-min, 105-dB SPL, 10-kHz pure tone) and permanent (PTS: 1-h, 105-dB SPL, 10-kHz octave band noise) threshold-shift protocols were used. The brief TTS exposure produced reversible reductions in DPOAEs that for both the B6.CAST and CAST mice recovered to within a few dB of their baseline levels by 3 min post-exposure. In contrast, the C57 mice recovered somewhat slower and, by 5 min post-exposure, emission levels were still 5 dB or more below their corresponding pre-exposure values. At 3 months of age, the TTS mice along with another group of naïve subjects representing the same three mouse strains were exposed to the PTS paradigm. By 4 days post-exposure, for B6.CAST and CAST mice, DPOAE levels had recovered to their pre-exposure control levels. However, DPOAEs for the C57 mice at most of the measurable frequencies were at least 10-30 dB lower than their counterpart baseline levels. Together these data suggest that the Ahl allele in the C57 strain contributes to both the early onset AHL exhibited by these mice as well as their susceptibility to both TTS and PTS over-exposures.
在同基因小鼠品系B6.CAST+Ahl(B6.CAST)中检测了耳蜗功能以及对噪声过度暴露的易感性,并将这些特征与CAST/Ei(CAST)和C57BL/6J(C57)亲本品系中的相同特征进行了比较。对于这两种类型的比较,主要测量指标是2f1-2f2处的畸变产物耳声发射(DPOAE)。我们的假设是,B6.CAST小鼠通过其另一亲本品系(CAST)的抗年龄特性,纠正了其亲本品系之一(C57)所表现出的早发性年龄相关性听力损失(AHL),因此既不会表现出AHL,也不会对噪声过度刺激效应敏感。关于耳蜗功能,对于2.5个月大的小鼠,C57和B6.CAST小鼠的中频主音调的DPOAE均有略低的趋势,而前者在最高测试频率下显示出明显的AHL效应。然而,到5个月大时,B6.CAST小鼠与CAST小鼠一样,显示出强劲的DPOAE水平,显著高于C57小鼠的DPOAE水平,C57小鼠在约30 kHz以上的频率基本上没有DPOAE。为了研究Ahl基因在耳蜗对噪声过度暴露影响的易感性中的作用,使用了两种不同的范式,包括短暂(TTS:1分钟,105 dB SPL,10 kHz纯音)和永久性(PTS:1小时,105 dB SPL,10 kHz倍频程带噪声)阈值偏移方案。短暂的TTS暴露使DPOAE出现可逆性降低,B6.CAST和CAST小鼠在暴露后3分钟内恢复到基线水平的几个分贝范围内。相比之下,C57小鼠恢复得稍慢,在暴露后5分钟,发射水平仍比其相应的暴露前值低5 dB或更多。在3个月大时,TTS小鼠与另一组代表相同三种小鼠品系的未处理受试者一起接受PTS范式。暴露后4天,B6.CAST和CAST小鼠的DPOAE水平恢复到暴露前对照水平。然而,C57小鼠在大多数可测量频率下的DPOAE比其相应的基线水平至少低10-30 dB。这些数据共同表明,C57品系中的Ahl等位基因导致了这些小鼠表现出的早发性AHL以及它们对TTS和PTS过度暴露的易感性。