ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Mutation of Foxo3 causes adult onset auditory neuropathy and alters cochlear synapse architecture in mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 55 citations in OpenAlex.
- A Diphtheria Toxin-Induced Mouse Model of Auditory Neuropathy: From Cochlear Synaptopathy to Neuronal Degeneration.Journal of the Association for Research in Otolaryngology : JARO · 2026Article
- Strengthening Medial Olivocochlear Feedback Reduces the Developmental Impact of Early Noise Exposure.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- A Decoy Oligodeoxynucleotides Disturbing Forkhead Box O3 Mediated ctnna2 Transcriptional Repression Prevents Postoperative Neurocognitive Disorder in Mice.CNS neuroscience & therapeutics · 2025Article
- Strengthening Medial Olivocochlear Feedback Reduces the Developmental Impact of Early Noise Exposure.bioRxiv : the preprint server for biology · 2025Article
- Fluorescent Tagging of Endogenous FOXO for Live Imaging and Pull-Down Assays.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Cochlear Ribbon Synapses in Aged Gerbils.International journal of molecular sciences · 2024Article
- Cognitive Impairment in Multiple Sclerosis.Bioengineering (Basel, Switzerland) · 2023Review
- Increased central auditory gain in 5xFAD Alzheimer's disease mice as an early biomarker candidate for Alzheimer's disease diagnosis.Frontiers in neuroscience · 2023Article
- Cochlear ribbon synapse maturation requires Nlgn1 and Nlgn3.iScience · 2022Article
- Molecular and cytological profiling of biological aging of mouse cochlear inner and outer hair cells.Cell reports · 2022Article
- FOXO3/TGF-β signal-dependent ciliogenesis and cell functions during differentiation of temperature-sensitive mouse cochlear precursor hair cells.Histochemistry and cell biology · 2022Article
- Cellular autophagy, the compelling roles in hearing function and dysfunction.Frontiers in cellular neuroscience · 2022Review
- Pegylated Insulin-Like Growth Factor 1 attenuates Hair Cell Loss and promotes Presynaptic Maintenance of Medial Olivocochlear Cholinergic Fibers in the Cochlea of the Progressive Motor Neuropathy Mouse.Frontiers in neurology · 2022Article
- FOXG1 promotes aging inner ear hair cell survival through activation of the autophagy pathway.Autophagy · 2021Article
- A combined genome-wide association and molecular study of age-related hearing loss in H. sapiens.BMC medicine · 2021Article
- Role of FoxO transcription factors in aging and age-related metabolic and neurodegenerative diseases.Cell & bioscience · 2021Review
- Hearing impairment due toDisease models & mechanisms · 2020Article
- Preventing presbycusis in mice with enhanced medial olivocochlear feedback.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- SIRT3 promotes auditory function in young adult FVB/nJ mice but is dispensable for hearing recovery after noise exposure.PloS one · 2020Article
- Hormone replacement therapy attenuates hearing loss: Mechanisms involving estrogen and the IGF-1 pathway.Aging cell · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Auditory neuropathy is a form of hearing loss in which cochlear inner hair cells fail to correctly encode or transmit acoustic information to the brain. Few genes have been implicated in the adult-onset form of this disease. Here we show that mice lacking the transcription factor Foxo3 have adult onset hearing loss with the hallmark characteristics of auditory neuropathy, namely, elevated auditory thresholds combined with normal outer hair cell function. Using histological techniques, we demonstrate that Foxo3-dependent hearing loss is not due to a loss of cochlear hair cells or spiral ganglion neurons, both of which normally express Foxo3. Moreover, Foxo3-knock-out (KO) inner hair cells do not display reductions in numbers of synapses. Instead, we find that there are subtle structural changes in and surrounding inner hair cells. Confocal microscopy in conjunction with 3D modeling and quantitative analysis show that synaptic localization is altered in Foxo3-KO mice and Myo7a immunoreactivity is reduced. TEM demonstrates apparent afferent degeneration. Strikingly, acoustic stimulation promotes Foxo3 nuclear localization in vivo, implying a connection between cochlear activity and synaptic function maintenance. Together, these findings support a new role for the canonical damage response factor Foxo3 in contributing to the maintenance of auditory synaptic transmission.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.