Thyroid hormone controls the timing of cochlear ribbon synapse maturation

• Published in: Biochemical and biophysical research communications Vol. 704; p. 149704
• Main Authors: Yu, Chaorong, He, Yihan, Liu, Qing, Qian, Xiaoyun, Gao, Xia, Yang, Deye, Yang, Ye, Wan, Guoqiang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.04.2024
• Subjects: Animals; Cochlea; epithelium; ganglia; gene targeting; Hearing - physiology; hyperthyroidism; hypothyroidism; Mice; Mice, Knockout; Pax8; postnatal development; Ribbon synapse; sodium; Spiral Ganglion; synapse; Synapses - physiology; Synaptic pruning; Thyroid hormone; thyroid hormone receptors; Thyroid Hormones; Synaptic pruning; Cochlea; Ribbon synapse; Thyroid hormone; Pax8
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2024.149704

Ribbon synapses in the cochlear hair cells are subject to extensive pruning and maturation processes before hearing onset. Previous studies have highlighted the pivotal role of thyroid hormone (TH) in this developmental process, yet the detailed mechanisms are largely unknown. In this study, we found that the thyroid hormone receptor α (Thrα) is expressed in both sensory epithelium and spiral ganglion neurons in mice. Hypothyroidism, induced by Pax8 gene knockout, significantly delays the synaptic pruning during postnatal development in mice. Detailed spatiotemporal analysis of ribbon synapse distribution reveals that synaptic maturation involves not only ribbon pruning but also their migration, both of which are notably delayed in the cochlea of Pax8 knockout mice. Intriguingly, postnatal hyperthyroidism, induced by intraperitoneal injections of liothyronine sodium (T3), accelerates the pruning of ribbon synapses to the mature state without affecting the auditory functions. Our findings suggest that thyroid hormone does not play a deterministic role but rather controls the timing of cochlear ribbon synapse maturation. •Cochlear ribbon synapses undergo extensive morphological maturation after birth.•Early postnatal hypothyroidism impairs the overall maturation of ribbon synapses.•Early postnatal hyperthyroidism results in accelerated pruning of ribbon synapses.•Synaptic pruning by hyperthyroidism is reversible and does not affect hearing.