Neuronal erythropoietin overexpression is protective against kanamycin-induced hearing loss in mice
| Autor: | Tim Honegger, David Bächinger, Lukas Horvath, Andreas H. Eckhard, Madeline M. Goosmann, Max Gassmann, Johannes Vogel, Arianne Monge Naldi |
|---|---|
| Přispěvatelé: | University of Zurich, Naldi, Arianne Monge |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Hearing loss Mice Transgenic 10045 Clinic for Otorhinolaryngology Toxicology Neuroprotection Mice 03 medical and health sciences Ototoxicity Kanamycin Internal medicine Hair Cells Auditory Evoked Potentials Auditory Brain Stem otorhinolaryngologic diseases medicine Animals Inner ear Hearing Loss High-Frequency Erythropoietin Spiral ganglion Neurons business.industry 3005 Toxicology General Medicine 10081 Institute of Veterinary Physiology medicine.disease Anti-Bacterial Agents Mice Inbred C57BL 030104 developmental biology Auditory brainstem response medicine.anatomical_structure Endocrinology 570 Life sciences biology Female sense organs Hair cell medicine.symptom Spiral Ganglion business medicine.drug |
| Zdroj: | Toxicology Letters. 291:121-128 |
| ISSN: | 0378-4274 |
| Popis: | Aminoglycosides have detrimental effects on the hair cells of the inner ear, yet these agents indisputably are one of the cornerstones in antibiotic therapy. Hence, there is a demand for strategies to prevent aminoglycoside-induced ototoxicity, which are not available today. In vitro data suggests that the pleiotropic growth factor erythropoietin (EPO) is neuroprotective against aminoglycoside-induced hair cell loss. Here, we use a mouse model with EPO-overexpression in neuronal tissue to evaluate whether EPO could also in vivo protect from aminoglycoside-induced hearing loss. Auditory brainstem response (ABR) thresholds were measured in 12-weeks-old mice before and after treatment with kanamycin for 15 days, which resulted in both C57BL/6 and EPO-transgenic animals in a high-frequency hearing loss. However, ABR threshold shifts in EPO-transgenic mice were significantly lower than in C57BL/6 mice (mean difference in ABR threshold shift 13.6 dB at 32 kHz, 95% CI 3.8–23.4 dB, p = 0.003). Correspondingly, quantification of hair cells and spiral ganglion neurons by immunofluorescence revealed that EPO-transgenic mice had a significantly lower hair cell and spiral ganglion neuron loss than C57BL/6 mice. In conclusion, neuronal overexpression of EPO is protective against aminoglycoside-induce hearing loss, which is in accordance with its known neuroprotective effects in other organs, such as the eye or the brain. |
| Databáze: | OpenAIRE |
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