Age-related hearing loss: GABA, nicotinic acetylcholine and NMDA receptor expression changes in spiral ganglion neurons of the mouse.
Age-related hearing loss: GABA, nicotinic acetylcholine and NMDA receptor expression changes in spiral ganglion neurons of the mouse.
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DOI：
10.1016/j.neuroscience.2013.11.058
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发表时间：
2014-02-14
期刊：
影响因子：
3.3
通讯作者：
Su J
中科院分区：
文献类型：
--
作者：
Tang X;Zhu X;Ding B;Walton JP;Frisina RD;Su J
与听力损失相关的听力损失-老年性耳聋-是我们老年人口中头号沟通障碍和最普遍的神经退行性疾病。虽然对于老年性耳聋患者来说，在背景噪声中理解语音是相当困难的，但目前还没有生物医学治疗方法来预防、延迟或逆转这种情况。更好地了解老年性耳聋的耳蜗机制将有助于未来的治疗。本研究采用免疫组化和半定量RT-PCR技术，观察CBA/CaJ小鼠耳蜗螺旋神经节神经元γ-氨基丁酸A（GABAA）受体α1亚单位、烟碱乙酰胆碱（nACh）受体β2亚单位和N-甲基-D-天冬氨酸（NMDA）受体NR 1亚单位mRNA和蛋白表达的变化。我们发现，与年轻的成年人相比，老年小鼠的听觉脑干反应（ABR）阈值在3-48 kHz范围内偏移超过40 dB。老年小鼠的DPOAE阈值在6-49 kHz范围内也发生了40 dB以上的偏移，其振幅在同一频率范围内明显降低或消失。螺旋神经节神经元（SGN）密度在基弯、中弯和顶弯均随年龄增长而下降，其中基弯SGN密度下降幅度最大。SGN密度与ABR波1振幅呈正相关。老年小鼠耳蜗SGN中GABAAR α1和AChR β2的mRNA和蛋白表达随年龄增长而降低。老年小鼠SGN中NMDAR NR 1的mRNA和蛋白表达随年龄增长而增加。这些结果表明CBA小鼠SGN中GABAAR、nAChR、NMDAR的表达存在与年龄相关的功能变化，反映了SGN的退化，这可能与耳蜗突触传递功能随年龄的变化有关，提示外周年龄相关性听力损失的生物学机制。
Age-related hearing loss – presbycusis – is the number one communication disorder and most prevalent neurodegenerative condition of our aged population. Although speech understanding in background noise is quite difficult for those with presbycusis, there are currently no biomedical treatments to prevent, delay or reverse this condition. A better understanding of the cochlear mechanisms underlying presbycusis will help lead to future treatments. Objectives of the present study were to investigate gamma-amino butyric acid A (GABAA) receptor subunit α1, nicotinic acetylcholine (nACh) receptor subunit β2, and N-methyl-D-aspartate (NMDA) receptor subunit NR1 mRNA and protein expression changes in spiral ganglion neurons of the CBA/CaJ mouse cochlea, that occur in age-related hearing loss, utilizing quantitative immunohistochemistry and semi-quantitative RT-PCR techniques. We found that auditory brainstem response (ABR) thresholds shifted over 40 dB from 3–48 kHz in old mice compared to young adults. DPOAE thresholds also shifted over 40 dB from 6–49 kHz in old mice, and their amplitudes were significantly decreased or absent in the same frequency range. Spiral ganglion neuron (SGN) density decreased with age in basal, middle and apical turns, and SGN density of the basal turn declined the most. A positive correlation was observed between SGN density and ABR wave 1 amplitude. mRNA and protein expression of GABAAR α1 and AChR β2 decreased with age in SGNs in the old mouse cochlea. mRNA and protein expression of NMDAR NR1 increased with age in SGNs of the old mice. These findings demonstrate that there are functionally-relevant age-related changes of GABAAR, nAChR, NMDAR expression in CBA mouse SGNs reflecting their degeneration, which may be related to functional changes in cochlear synaptic transmission with age, suggesting biological mechanisms for peripheral age-related hearing loss.
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影响因子：
3
作者：
D'Souza, Mary;Zhu, Xiaoxia;Frisina, Robert D.
通讯作者：
Frisina, Robert D.
影响因子：
5.3
作者：
Kujawa, SG;Liberman, MC
通讯作者：
Liberman, MC
影响因子：
16.2
作者：
Oliver, D;Klöcker, N;Fakler, B
通讯作者：
Fakler, B
DOI：
10.1523/jneurosci.2845-09.2009
发表时间：
2009-11-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kujawa SG;Liberman MC
通讯作者：
Liberman MC
影响因子：
4.2
作者：
Caspary DM;Hughes LF;Ling LL
通讯作者：
Ling LL