ArticleMolecular neurobiology2016
Deterioration of the Medial Olivocochlear Efferent System Accelerates Age-Related Hearing Loss in Pax2-Isl1 Transgenic Mice.
Article in Molecular neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 21 citations in OpenAlex.
- Conditional Deletion of Isl1 Disrupts Cochlear Sensory and Neuronal Development, Leading to Hearing Loss.Molecular neurobiology · 2026Article
- Virally mediated enhancement of efferent inhibition reduces acoustic trauma in wild-type murine cochleas.Molecular therapy. Methods & clinical development · 2025Article
- ISL1 is necessary for auditory neuron development and contributes toward tonotopic organization.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Age-Related Hearing Loss: Sensory and Neural Etiology and Their Interdependence.Frontiers in aging 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
- Overexpression ofInternational journal of molecular sciences · 2021Article
- Transcription Factor Reprogramming in the Inner Ear: Turning on Cell Fate Switches to Regenerate Sensory Hair Cells.Frontiers in cellular neuroscience · 2021Article
- Molecular Aspects of the Development and Function of Auditory Neurons.International journal of molecular sciences · 2020Review
- Rathke's cleft-like cysts arise from Isl1 deletion in murine pituitary progenitors.The Journal of clinical investigation · 2020Article
- Early ear neuronal development, but not olfactory or lens development, can proceed without SOX2.Developmental biology · 2020Article
- Neurod1 Is Essential for the Primary Tonotopic Organization and Related Auditory Information Processing in the Midbrain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Enhancement of the Medial Olivocochlear System Prevents Hidden Hearing Loss.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Olivocochlear efferents: Their action, effects, measurement and uses, and the impact of the new conception of cochlear mechanical responses.Hearing research · 2018Review
- Olivocochlear Efferents in Animals and Humans: From Anatomy to Clinical Relevance.Frontiers in neurology · 2018Review
- Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation.Molecular neurobiology · 2017Article
- Minimal Effects of Age and Exposure to a Noisy Environment on Hearing in Alpha9 Nicotinic Receptor Knockout Mice.Frontiers in neuroscience · 2017Article
- Incomplete and delayed Sox2 deletion defines residual ear neurosensory development and maintenance.Scientific reports · 2016Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development, maturation, and maintenance of the inner ear are governed by temporal and spatial expression cascades of transcription factors that form a gene regulatory network. ISLET1 (ISL1) may be one of the major players in this cascade, and in order to study its role in the regulation of inner ear development, we produced a transgenic mouse overexpressing Isl1 under the Pax2 promoter. Pax2-regulated ISL1 overexpression increases the embryonic ISL1(+) domain and induces accelerated nerve fiber extension and branching in E12.5 embryos. Despite these gains in early development, the overexpression of ISL1 impairs the maintenance and function of hair cells of the organ of Corti. Mutant mice exhibit hyperactivity, circling behavior, and progressive age-related decline in hearing functions, which is reflected in reduced otoacoustic emissions (DPOAEs) followed by elevated hearing thresholds. The reduction of the amplitude of DPOAEs in transgenic mice was first detected at 1 month of age. By 6-9 months of age, DPOAEs completely disappeared, suggesting a functional inefficiency of outer hair cells (OHCs). The timing of DPOAE reduction coincides with the onset of the deterioration of cochlear efferent terminals. In contrast to these effects on efferents, we only found a moderate loss of OHCs and spiral ganglion neurons. For the first time, our results show that the genetic alteration of the medial olivocochlear (MOC) efferent system induces an early onset of age-related hearing loss. Thus, the neurodegeneration of the MOC system could be a contributing factor to the pathology of age-related hearing loss.
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