title: Neuronal erythropoietin overexpression protects mice against age-related hearing loss (presbycusis).
abstract: So far, typical causes of presbycusis such as degeneration of hair cells and/or primary auditory (spiral ganglion) neurons cannot be treated. Because erythropoietin's (Epo) neuroprotective potential has been shown previously, we determined hearing thresholds of juvenile and aged mice overexpressing Epo in neuronal tissues. Behavioral audiometry revealed in contrast to 5 months of age, that 11-month-old Epo-transgenic mice had up to 35 dB lower hearing thresholds between 1.4 and 32 kHz, and at the highest frequencies (50-80 kHz), thresholds could be obtained in aged Epo-transgenic only but not anymore in old C57BL6 control mice. Click-evoked auditory brainstem response showed similar results. Numbers of spiral ganglion neurons in aged C57BL6 but not Epo-transgenic mice were dramatically reduced mainly in the basal turn, the location of high frequencies. In addition, there was a tendency to better preservation of inner and outer hair cells in Epo-transgenic mice. Hence, Epo's known neuroprotective action effectively suppresses the loss of spiral ganglion cells and probably also hair cells and, thus, development of presbycusis in mice.
authors.affiliation: Department of Inner Ear Research, Clinic for Otolaryngology, Head and Neck Surgery, University Hospital Zürich, University of Zürich, Zürich, Switzerland.
authors.forename: Arianne
authors.initials: A
authors.lastname: Monge Naldi
authors.affiliation: Department of Inner Ear Research, Clinic for Otolaryngology, Head and Neck Surgery, University Hospital Zürich, University of Zürich, Zürich, Switzerland; Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.
authors.forename: Celina
authors.initials: C
authors.lastname: Belfrage
authors.affiliation: Department of Biomedicine, University Hospital Basel, Clinic for Otolaryngology, Head and Neck Surgery, University of Basel, Basel, Switzerland.
authors.forename: Neha
authors.initials: N
authors.lastname: Jain
authors.affiliation: Department of Biomedicine, University Hospital Basel, Clinic for Otolaryngology, Head and Neck Surgery, University of Basel, Basel, Switzerland.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Wei
authors.affiliation: Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.
authors.forename: Belén
authors.initials: B
authors.lastname: Canto Martorell
authors.affiliation: Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland; Zürich Center for Integrative Human Physiology (ZIHP), University of Zürich, Zürich, Switzerland; Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru.
authors.forename: Max
authors.initials: M
authors.lastname: Gassmann
authors.affiliation: Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland. Electronic address: jvogel@vetphys.uzh.ch.
authors.forename: Johannes
authors.initials: J
authors.lastname: Vogel
mesh_terms: D000818:Animals; D004921:Erythropoietin / Q000235:genetics* / Q000502:physiology*; D005072:Evoked Potentials, Auditory / Q000502:physiology; D015870:Gene Expression / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006198:Hair Cells, Auditory / Q000473:pathology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009410:Nerve Degeneration; D018696:Neuroprotective Agents; D011304:Presbycusis / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D013136:Spiral Ganglion / Q000166:cytology / Q000473:pathology
chemical_list: D018696:Neuroprotective Agents; D004921:Erythropoietin
keywords: ABR; Age-related hearing loss (ARHL); Cochlea; Excitotoxicity; Neuroprotection; Spiral ganglion