Neuronal erythropoietin overexpression is protective against kanamycin-induced hearing loss in mice. (July 2018)

• Record Type: Journal Article
• Authors: Bächinger, David; Horvath, Lukas; Eckhard, Andreas; Goosmann, Madeline M.; Honegger, Tim; Gassmann, Max; Vogel, Johannes; Naldi, Arianne Monge
• Is Part Of: Toxicology letters. Volume 291(2018)
• Page Start: 121
• Page End: 128
• Publication Date: 2018-07
• Subjects: EPO -- Neuroprotection -- Hair cells -- Spiral ganglion neurons -- Kanamycin -- Aminoglycoside-induced hearing loss -- Ototoxicity -- Cochleotoxicity -- ABR; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2018.04.007
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: The protective effect of erythropoietin against aminoglycoside-induced hearing loss was studied in mice. Neuronal erythropoietin overexpression protected against aminoglycoside-induced hearing loss. Neuronal erythropoietin overexpression reduced hair cell and spiral ganglion neuron loss. Abstract: 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.