Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Cell Death Dis. 2023 Sep 13;14(9):605. doi: 10.1038/s41419-023-06100-8.
Hearing loss impacts the quality of life and affects communication resulting in social isolation and reduced well-being. Despite its impact on society and economy, no therapies for age-related hearing loss are available so far. Loss of mechanosensory hair cells of the cochlea is a common event of hearing loss in humans. Studies performed in birds demonstrating that they can be replaced following the proliferation and transdifferentiation of supporting cells, strongly pointed out on HCs regeneration as the main focus of research aimed at hearing regeneration. Neurotrophins are growth factors involved in neuronal survival, development, differentiation, and plasticity. NGF has been involved in the interplay between auditory receptors and efferent innervation in the cochlea during development. During embryo development, both NGF and its receptors are highly expressed in the inner ears. It has been reported that NGF is implicated in the differentiation of auditory gangliar and hair cells. Thus, it has been proposed that NGF administration can decrease neuronal damage and prevent hearing loss. The main obstacle to the development of hearing impairment therapy is that efficient means of delivery for selected drugs to the cochlea are missing. Herein, in this study NGF was administered by the intranasal route. The first part of the study was focused on a biodistribution study, which showed the effective delivery in the cochlea; while the second part was focused on analyzing the potential therapeutic effect of NGF in senescence-accelerated prone strain 8 mice. Interestingly, intranasal administration of NGF resulted protective in counteracting hearing impairment in SAMP8 mice, ameliorating hearing performances (analyzed by auditory brainstem responses and distortion product otoacoustic emission) and hair cells morphology (analyzed by microscopy analysis). The results obtained were encouraging indicating that the neurotrophin NGF was efficiently delivered to the inner ear and that it was effective in counteracting hearing loss.
听力损失影响生活质量，并影响交流，导致社交孤立和幸福感降低。尽管它对社会和经济有影响，但迄今为止还没有治疗与年龄相关的听力损失的方法。耳蜗机械感觉毛细胞的丧失是人类听力损失的常见事件。鸟类研究表明，支持细胞的增殖和转分化后可以替代它们，这强烈指出了 HC 再生是听力再生研究的主要焦点。神经营养因子是参与神经元存活、发育、分化和可塑性的生长因子。NGF 参与了耳蜗中听觉受体和传出神经支配之间的相互作用在发育过程中。在胚胎发育过程中，NGF 及其受体在内耳中高度表达。据报道，NGF 参与了听神经节和毛细胞的分化。因此，有人提出，NGF 的给药可以减少神经元损伤并预防听力损失。听力损伤治疗发展的主要障碍是缺乏将选定药物有效递送到耳蜗的方法。在此，在这项研究中，NGF 通过鼻内途径给药。研究的第一部分侧重于生物分布研究，该研究显示了在耳蜗中的有效传递；而第二部分则侧重于分析 NGF 在快速衰老品系 8 小鼠中的潜在治疗效果。有趣的是，NGF 的鼻内给药在对抗 SAMP8 小鼠的听力损伤方面具有保护作用，改善了听力表现（通过听觉脑干反应和畸变产物耳声发射分析）和毛细胞形态（通过显微镜分析分析）。获得的结果令人鼓舞，表明神经营养因子 NGF 被有效地递送到内耳，并且在对抗听力损失方面是有效的。
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