ArticleMolecular neurobiology2015
Inhibition of the activation and recruitment of microglia-like cells protects against neomycin-induced ototoxicity.
Article in Molecular neurobiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- Thioredoxin protects against diabetic hearing loss by regulating TOMM22 mediated mitochondrial autophagy in hair cells and inhibiting microglial M1 polarization.Scientific reports · 2026Article
- MEK/ERK signaling drives the transdifferentiation of supporting cells into functional hair cells by modulating the Notch pathway.Stem cells translational medicine · 2024Article
- NADPH Oxidase 3: Beyond the Inner Ear.Antioxidants (Basel, Switzerland) · 2024Review
- Identification and Characterization of TMEM119-Positive Cells in the Postnatal and Adult Murine Cochlea.Brain sciences · 2023Article
- Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model.Journal of otology · 2023Article
- Macrophage-related immune responses in inner ear: a potential therapeutic target for sensorineural hearing loss.Frontiers in neuroscience · 2023Review
- 6'-sialyllactose ameliorates the ototoxic effects of the aminoglycoside antibiotic neomycin in susceptible mice.Frontiers in immunology · 2023Article
- Heterogeneity in macrophages along the cochlear spiral in mice: insights from SEM and functional analyses.Frontiers in cellular neuroscience · 2023Article
- Extracellular Vesicles in Inner Ear Therapies-Pathophysiological, Manufacturing, and Clinical Considerations.Journal of clinical medicine · 2022Review
- Intratympanic Administration of Dieckol Prevents Ototoxic Hearing Loss.Marine drugs · 2022Article
- The protective effects of systemic dexamethasone on sensory epithelial damage and hearing loss in targeted Cx26-null mice.Cell death & disease · 2022Article
- Hippo/YAP signaling pathway protects against neomycin-induced hair cell damage in the mouse cochlea.Cellular and molecular life sciences : CMLS · 2022Article
- CX3CR1 mutation alters synaptic and astrocytic protein expression, topographic gradients, and response latencies in the auditory brainstem.The Journal of comparative neurology · 2021Article
- The Detrimental and Beneficial Functions of Macrophages After Cochlear Injury.Frontiers in cell and developmental biology · 2021Review
- Innate Immunity to Spiral Ganglion Neuron Loss: A Neuroprotective Role of Fractalkine Signaling in Injured Cochlea.Frontiers in cellular neuroscience · 2021Review
- Macrophages Are Dispensable for Postnatal Pruning of the Cochlear Ribbon Synapses.Frontiers in cellular neuroscience · 2021Article
- Redox activation of excitatory pathways in auditory neurons as mechanism of age-related hearing loss.Redox biology · 2020Article
- Citicoline Protects Auditory Hair Cells Against Neomycin-Induced Damage.Frontiers in cell and developmental biology · 2020Article
- Autoinflammatory characteristics and short-term effects of delivering high-dose steroids to the surface of the intact endolymphatic sac and incus in refractory Ménière's disease.Journal of otology · 2019Article
- Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use.Scientific reports · 2019Article
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One of the most unfortunate side effects of aminoglycoside (AG) antibiotics such as neomycin is that they target sensory hair cells (HCs) and can cause permanent hearing impairment. We have observed HC loss and microglia-like cell (MLC) activation in the inner ear (cochlea) following neomycin administration. We focused on CX3CL1, a membrane-bound glycoprotein expressed on neurons and endothelial cells, as a way to understand how the MLCs are activated and the role these cells play in HC loss. CX3CL1 is the exclusive ligand for CX3CR1, which is a chemokine receptor expressed on the surface of macrophages and MLCs. In vitro experiments showed that the expression levels of CX3CL1 and CX3CR1 increased in the cochlea upon neomycin treatment, and CX3CL1 was expressed on HCs, while CX3CR1 was expressed on MLCs. When cultured with 1 μg/mL exogenous CX3CL1, MLCs were activated by CX3CL1, and the cytokine level was increased in the cochleae leading to apoptosis in the HCs. In CX3CR1 knockout mice, a significantly greater number of cochlear HCs survived than in wild-type mice when the cochlear explants were cultured with neomycin in vitro. Furthermore, inhibiting the activation of MLCs with minocycline reduced the neomycin-induced HC loss and improved the hearing function in neomycin-treated mice in vivo. Our results demonstrate that CX3CL1-induced MLC activation plays an important role in the induction of HC death and provide evidence for CX3CL1 and CX3CR1 as promising new therapeutic targets for the prevention of hearing loss.
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