Aminoglycoside-Induced Hair Cell Death of Inner Ear Organs Causes Functional Deficits in Adult Zebrafish (Danio rerio)

Phillip M. Uribe, Huifang Sun, Kevin Wang, James D. Asuncion, Qi Wang, Chien Wei Chen, Peter Steyger, Michael E. Smith, Jonathan I. Matsui

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Aminoglycoside antibiotics, like gentamicin, kill inner ear sensory hair cells in a variety of species including chickens, mice, and humans. The zebrafish (Danio rerio) has been used to study hair cell cytotoxicity in the lateral line organs of larval and adult animals. Little is known about whether aminoglycosides kill the hair cells within the inner ear of adult zebrafish. We report here the ototoxic effects of gentamicin on hair cells in the saccule, the putative hearing organ, and utricle of zebrafish. First, adult zebrafish received a single 30 mg/kg intraperitoneal injection of fluorescently-tagged gentamicin (GTTR) to determine the distribution of gentamicin within inner ear sensory epithelia. After 4 hours, GTTR was observed in hair cells throughout the saccular and utriclar sensory epithelia. To assess the ototoxic effects of gentamicin, adult zebrafish received a single 250 mg/kg intraperitoneal injection of gentamicin and, 24 hours later, auditory evoked potential recordings (AEPs) revealed significant shifts in auditory thresholds compared to untreated controls. Zebrafish were then euthanized, the inner ear fixed, and labeled for apoptotic cells (TUNEL reaction), and the stereociliary bundles of hair cells labeled with fluorescently-tagged phalloidin. Whole mounts of the saccule and utricle were imaged and cells counted. There were significantly more TUNEL-labeled cells found in both organs 4 hours after gentamicin injection compared to vehicle-injected controls. As expected, significantly fewer hair cell bundles were found along the rostral-caudal axis of the saccule and in the extrastriolar and striolar regions of the utricle in gentamicin-treated animals compared to untreated controls. Therefore, as in other species, gentamicin causes significant inner ear sensory hair cell death and auditory dysfunction in zebrafish.

Original languageEnglish (US)
Article numbere58755
JournalPLoS One
Volume8
Issue number3
DOIs
StatePublished - Mar 22 2013

Fingerprint

aminoglycosides
Aminoglycosides
Zebrafish
Inner Ear
Cell death
Gentamicins
Danio rerio
gentamicin
hairs
cell death
ears
Cell Death
Saccule and Utricle
Cells
cells
In Situ Nick-End Labeling
intraperitoneal injection
Intraperitoneal Injections
Animals
epithelium

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Uribe, P. M., Sun, H., Wang, K., Asuncion, J. D., Wang, Q., Chen, C. W., ... Matsui, J. I. (2013). Aminoglycoside-Induced Hair Cell Death of Inner Ear Organs Causes Functional Deficits in Adult Zebrafish (Danio rerio). PLoS One, 8(3), [e58755]. https://doi.org/10.1371/journal.pone.0058755

Aminoglycoside-Induced Hair Cell Death of Inner Ear Organs Causes Functional Deficits in Adult Zebrafish (Danio rerio). / Uribe, Phillip M.; Sun, Huifang; Wang, Kevin; Asuncion, James D.; Wang, Qi; Chen, Chien Wei; Steyger, Peter; Smith, Michael E.; Matsui, Jonathan I.

In: PLoS One, Vol. 8, No. 3, e58755, 22.03.2013.

Research output: Contribution to journalArticle

Uribe, Phillip M. ; Sun, Huifang ; Wang, Kevin ; Asuncion, James D. ; Wang, Qi ; Chen, Chien Wei ; Steyger, Peter ; Smith, Michael E. ; Matsui, Jonathan I. / Aminoglycoside-Induced Hair Cell Death of Inner Ear Organs Causes Functional Deficits in Adult Zebrafish (Danio rerio). In: PLoS One. 2013 ; Vol. 8, No. 3.
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