Each neuromast contains sensory hair cells and non-sensory supporting cells that project into the aquatic environment making it very convenient to study the effects of drugs on sensory hair cells in vivo. Zebrafish can detect auditory frequencies between 100 Hz and 4000 Hz, , and also have a lateral line system that detects changes in water flow and is composed of neuromasts along the fish’s head and body. The zebrafish saccule, as in other teleosts, is thought to process auditory information.
While zebrafish do not have a dedicated auditory organ like the mammalian cochlea, they have otolithic vestibular organs such as the saccule and utricle that are similar to mammalian vestibular organs. Zebrafish ( Danio rerio) have become an established animal model to study sensory hair cell death, ,, ,, ,, ,, ,, ,,. Aminoglycoside antibiotics, like gentamicin, are a class of commonly-prescribed and essential antibiotics used to treat severe gram-negative bacterial infections, but they can cause permanent loss of sensory hair cells in humans and other mammals. Loss of these receptors from excessive noise, ototoxic pharmaceutical agents, and aging can lead to permanent hearing loss and vestibular deficits in humans. Sensory hair cells are mechanoreceptors within the inner ear that transduce sound and head movements into neural signals making them essential for hearing and balance. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials as outlined in the guide for authors. Matsui, is a PLOS ONE Editorial Board member. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The senior author of this manuscript, Jonathan I. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This project was supported by a Pomona College SURP (KW), A Rose Hills Foundation Summer Science and Engineering Research Fellowship (CWC), and National Institutes of Health grants DC04555 (PSS), P20RR16481 and P20GM103436-12 (MES), and DC010998 (JIM). Received: JanuAccepted: FebruPublished: March 22, 2013Ĭopyright: © 2013 Uribe et al. Texas A&M University, United States of America (2013) Aminoglycoside-Induced Hair Cell Death of Inner Ear Organs Causes Functional Deficits in Adult Zebrafish ( Danio rerio).
Therefore, as in other species, gentamicin causes significant inner ear sensory hair cell death and auditory dysfunction in zebrafish.Ĭitation: Uribe PM, Sun H, Wang K, Asuncion JD, Wang Q, Chen C-W, et al. 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. There were significantly more TUNEL-labeled cells found in both organs 4 hours after gentamicin injection compared to vehicle-injected controls. Whole mounts of the saccule and utricle were imaged and cells counted. 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. 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. After 4 hours, GTTR was observed in hair cells throughout the saccular and utriclar sensory epithelia. 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. We report here the ototoxic effects of gentamicin on hair cells in the saccule, the putative hearing organ, and utricle of zebrafish.
Little is known about whether aminoglycosides kill the hair cells within the inner ear of adult zebrafish. The zebrafish ( Danio rerio) has been used to study hair cell cytotoxicity in the lateral line organs of larval and adult animals. Aminoglycoside antibiotics, like gentamicin, kill inner ear sensory hair cells in a variety of species including chickens, mice, and humans.
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