ArticleInternational journal of molecular sciences2025
A Single Dose of AC102 Reverts Tinnitus by Restoring Ribbon Synapses in Noise-Exposed Mongolian Gerbils.
Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Application of neurodegenerative disease treatment strategies in tinnitus: mechanisms, translation, and prospects.Frontiers in aging neuroscience · 2026Review
- 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) induces early hearing loss in guinea pigs via activating AhR to trigger mitochondrial and endoplasmic reticulum stress-regulated autophagy.Archives of toxicology · 2025Article
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5 authors.
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Abstract
A single intratympanic application of the small-molecule drug AC102 was previously shown to promote significant recovery of hearing thresholds in a noise-induced hearing loss model in guinea pigs. Here, we report the effects of AC102 to revert synaptopathy of inner hair cells (IHCs) and behavioral signs of tinnitus in Mongolian gerbils following mild noise trauma. This experimental protocol led to minor hearing threshold shifts with no loss of auditory hair cells (HCs) but induced synaptopathy and a sustained and significant tinnitus percept. Treatment by intratympanic application of AC102 was evaluated in two protocols: 1. three weekly injections or 2. a single application. We evaluated hearing threshold changes using the auditory brainstem response (ABR) and the development of a tinnitus percept using the gap prepulse inhibition of acoustic startle (GPIAS) behavioral response. The number of IHC ribbon synapses along the cochlear frequency map were counted by immunostaining for the synaptic ribbon protein carboxy-terminal binding protein 2 (CTBP2). AC102 strongly and significantly reduced behavioral signs of tinnitus, as reflected by altered GPIAS. Noise-induced loss of IHC ribbon synapses was significantly reduced by AC102 compared to vehicle-treated ears. These results demonstrate that a single application of AC102 restores ribbon synapses following mild noise trauma thereby promoting recovery from tinnitus-related behavioral responses in vivo.
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