FGF13 prevents age-related hearing loss by protecting spiral ganglion neurons and ribbon synapses from injury

Cell Death Discov. 2025 Jul 5;11(1):307. doi: 10.1038/s41420-025-02607-5.

Abstract

Age-related hearing loss (ARHL) is the most common sensorineural hearing loss, and the dysfunction of spiral ganglion neurons (SGNs) and ribbon synapses plays a crucial role in the pathogenesis. The fibroblast growth factor 13 (FGF13) is considered to be associated with neuronal survival and synaptic transmission. However, whether FGF13 is involved in degeneration of SGNs and ribbon synapses, the typical changes of ARHL, is still unknown. Firstly, the expression of FGF13 mRNA and protein, was all dramatically decreased in the SGNs of aged mice, accompanied by impaired SGNs and ribbon synapses. More importantly, specific upregulation of FGF13 in SGNs significantly reduced hearing threshold, improved wave I amplitude, and alleviated loss of SGNs as well as ribbon synapses. Furthermore, the proteomic analysis and verification results suggested that the decrease of FGF13 induced the loss of SGNs and ribbon synapses partly by regulating the ORC1. Taken together, our data revealed that FGF13 might protect SGNs and ribbon synapses by regulating the expression of ORC1, which could provide a new idea and targets for the prevention and treatment of ARHL.