Department of Otorhinolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Jiao Tong University School of Medicine Ear Institute, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
Shanghai Jiao Tong University School of Medicine Ear Institute, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China; Department of Otorhinolaryngology, Head and Neck Surgery, Affiliated Hospital of Yanbian University, Yanji, Jilin, China.
Biochem Biophys Res Commun. 2023 May 7;655:68-74. doi: 10.1016/j.bbrc.2023.03.026. Epub 2023 Mar 11.
Thyroid hormone deficiency can lead to abnormal auditory development of varying severity. Retardation of morphological development, including delays in degeneration of Kölliker's organ and subsequent delayed formation of the inner sulcus, along with delayed opening of the tunnel of Corti and malformation of the tectorial membrane, was consistently observed in an antithyroid drug-induced congenital hypothyroidism rodent model. Abnormal morphological development could partly explain impaired adult auditory function. However, whether the development of inner hair cell ribbon synapses is influenced by hypothyroidism remains unclear. In the present study, we characterize the normal degeneration pattern of Kölliker's organ along the basal-to-apical axis. Then, we verified the retardation of morphological development in congenital hypothyroid mice. Using this model, we found that twisted collagen is present in the major tectorial membrane and delayed separation from supporting cells affects the minor tectorial membrane. Finally, we found that the number of synaptic ribbons was not significantly altered but the ribbon synapse maturation process was significantly impaired in congenital hypothyroid mice. We conclude that thyroid hormone is involved in structural development of the tectorial membrane and the ribbon synapse maturation process.
甲状腺激素缺乏可导致听觉发育异常,严重程度不一。在抗甲状腺药物诱导的先天性甲状腺功能减退症啮齿动物模型中,形态发育延迟,包括科利克氏器退化延迟以及随后的内沟形成延迟、柯蒂氏隧道开放延迟和盖膜畸形,均一致观察到。异常的形态发育部分解释了成年听觉功能受损的原因。然而,甲状腺功能减退是否影响内毛细胞带状突触的发育尚不清楚。在本研究中,我们描述了科利克氏器沿基底至顶侧轴的正常退化模式。然后,我们验证了先天性甲状腺功能减退小鼠的形态发育延迟。使用该模型,我们发现主要盖膜中存在扭曲的胶原,支持细胞的延迟分离会影响小盖膜。最后,我们发现先天性甲状腺功能减退小鼠的突触带数量没有明显改变,但带突触成熟过程明显受损。我们的结论是,甲状腺激素参与了盖膜的结构发育和带状突触的成熟过程。