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在患有早发性进行性听力损失的小鼠中,听觉神经突触在听觉输入丧失很久之后仍持续存在于蜗腹侧核中。

Auditory nerve synapses persist in ventral cochlear nucleus long after loss of acoustic input in mice with early-onset progressive hearing loss.

作者信息

McGuire Brian, Fiorillo Benjamin, Ryugo David K, Lauer Amanda M

机构信息

Center for Hearing and Balance and Department of Otolaryngology-HNS, Johns Hopkins University, Baltimore, MD 21205, USA.

Hearing Research Unit, Garvan Institute of Medical Research, Darlinghurst 2010, NSW, Australia; School of Medical Sciences, University of New South Wales, Kensington 2052, NSW, Australia.

出版信息

Brain Res. 2015 Apr 24;1605:22-30. doi: 10.1016/j.brainres.2015.02.012. Epub 2015 Feb 14.

Abstract

Perceptual performance in persons with hearing loss, especially those using devices to restore hearing, is not fully predicted by traditional audiometric measurements designed to evaluate the status of peripheral function. The integrity of auditory brainstem synapses may vary with different forms of hearing loss, and differential effects on the auditory nerve-brain interface may have particularly profound consequences for the transfer of sound from ear to brain. Loss of auditory nerve synapses in ventral cochlear nucleus (VCN) has been reported after acoustic trauma, ablation of the organ of Corti, and administration of ototoxic compounds. The effects of gradually acquired forms deafness on these synapses are less well understood. We investigated VCN gross morphology and auditory nerve synapse integrity in DBA/2J mice with early-onset progressive sensorineural hearing loss. Hearing status was confirmed using auditory brainstem response audiometry and acoustic startle responses. We found no change in VCN volume, number of macroneurons, or number of VGLUT1-positive auditory nerve terminals between young adult and older, deaf DBA/2J. Cell-type specific analysis revealed no difference in the number of VGLUT1 puncta contacting bushy and multipolar cell body profiles, but the terminals were smaller in deaf DBA/2J mice. Transmission electron microscopy confirmed the presence of numerous healthy, vesicle-filled auditory nerve synapses in older, deaf DBA/2J mice. The present results suggest that synapses can be preserved over a relatively long time-course in gradually acquired deafness. Elucidating the mechanisms supporting survival of central auditory nerve synapses in models of acquired deafness may reveal new opportunities for therapeutic intervention.

摘要

听力损失患者,尤其是那些使用听力恢复设备的患者,其感知性能并不能完全通过旨在评估外周功能状态的传统听力测量来预测。听觉脑干突触的完整性可能因不同形式的听力损失而有所不同,并且对听神经与脑接口的不同影响可能对声音从耳朵到大脑的传递产生特别深远的影响。据报道,在遭受声学创伤、切除柯蒂氏器以及使用耳毒性化合物后,腹侧耳蜗核(VCN)中的听神经突触会丧失。对于逐渐获得性耳聋对这些突触的影响,人们了解得较少。我们研究了患有早发性进行性感音神经性听力损失的DBA/2J小鼠的VCN大体形态和听神经突触完整性。使用听觉脑干反应测听法和听觉惊吓反应来确认听力状态。我们发现,在年轻成年和老年耳聋的DBA/2J小鼠之间,VCN体积、大神经元数量或VGLUT1阳性听神经终末数量没有变化。细胞类型特异性分析显示,与浓密型和多极型细胞体轮廓接触的VGLUT1斑点数量没有差异,但在耳聋的DBA/2J小鼠中,终末较小。透射电子显微镜证实,在老年耳聋的DBA/2J小鼠中存在大量健康的、充满囊泡的听神经突触。目前的结果表明,在逐渐获得性耳聋中,突触可以在相对较长的时间过程中得以保留。阐明在获得性耳聋模型中支持中枢听神经突触存活的机制,可能会揭示新的治疗干预机会。

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