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:
Zdroj: Toxicology Letters. 291:121-128
ISSN: 0378-4274
DOI: 10.1016/j.toxlet.2018.04.007
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