Zebrafish swimming behavior as a biomarker for ototoxicity-induced hair cell damage: A high-throughput drug development platform targeting hearing loss

Maki Niihori, Terry Platto, Suzu Igarashi, Audriana Hurbon, Allison M. Dunn, Phi Tran, Hung Tran, Jordan A. Mudery, Marvin J Slepian, Abraham Jacob

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Hearing loss is one of the most common human sensory disabilities, adversely affecting communication, socialization, mood, physical functioning, and quality of life. In addition to age and noise-induced damage, ototoxicity is a common cause of sensorineural hearing loss with chemotherapeutic agents, for example, cisplatin, being a major contributor. Zebrafish (Danio rerio) are an excellent model to study hearing loss as they have neurosensory hair cells on their body surface that are structurally similar to those within the human inner ear. Anatomic assays of toxin-mediated hair cell damage in zebrafish have been established; however, using fish swimming behavior - rheotaxis - as a biomarker for this anatomic damage was only recently described. We hypothesized that, in parallel, multilane measurements of rheotaxis could be used to create a high-throughput platform for drug development assessing both ototoxic and potentially otoprotective compounds in real time. Such a device was created, and results demonstrated a clear dose response between cisplatin exposure, progressive hair cell damage, and reduced rheotaxis in zebrafish. Furthermore, pre-exposure to the otoprotective medication dexamethasone, before cisplatin exposure, partially rescued rheotaxis swimming behavior and hair cell integrity. These results provide the first evidence that rescued swimming behavior can serve as a biomarker for rescued hair cell function. Developing a drug against hearing loss represents an unmet clinical need with global implications. Because hearing loss from diverse etiologies may result from common end-effects at the hair cell level, lessons learned from the present study may be broadly used.

Original languageEnglish (US)
Pages (from-to)440-450
Number of pages11
JournalTranslational Research
Volume166
Issue number5
DOIs
StatePublished - Nov 1 2015

Fingerprint

Audition
Biomarkers
Zebrafish
Hearing Loss
Cells
Throughput
Pharmaceutical Preparations
Cisplatin
Socialization
Sensorineural Hearing Loss
Inner Ear
Fish
Dexamethasone
Noise
Swimming
Assays
Fishes
Communication
Quality of Life
Equipment and Supplies

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, medical
  • Public Health, Environmental and Occupational Health

Cite this

Zebrafish swimming behavior as a biomarker for ototoxicity-induced hair cell damage : A high-throughput drug development platform targeting hearing loss. / Niihori, Maki; Platto, Terry; Igarashi, Suzu; Hurbon, Audriana; Dunn, Allison M.; Tran, Phi; Tran, Hung; Mudery, Jordan A.; Slepian, Marvin J; Jacob, Abraham.

In: Translational Research, Vol. 166, No. 5, 01.11.2015, p. 440-450.

Research output: Contribution to journalArticle

Niihori, Maki ; Platto, Terry ; Igarashi, Suzu ; Hurbon, Audriana ; Dunn, Allison M. ; Tran, Phi ; Tran, Hung ; Mudery, Jordan A. ; Slepian, Marvin J ; Jacob, Abraham. / Zebrafish swimming behavior as a biomarker for ototoxicity-induced hair cell damage : A high-throughput drug development platform targeting hearing loss. In: Translational Research. 2015 ; Vol. 166, No. 5. pp. 440-450.
@article{1681e183e7244842a8cc280e3915ca73,
title = "Zebrafish swimming behavior as a biomarker for ototoxicity-induced hair cell damage: A high-throughput drug development platform targeting hearing loss",
abstract = "Hearing loss is one of the most common human sensory disabilities, adversely affecting communication, socialization, mood, physical functioning, and quality of life. In addition to age and noise-induced damage, ototoxicity is a common cause of sensorineural hearing loss with chemotherapeutic agents, for example, cisplatin, being a major contributor. Zebrafish (Danio rerio) are an excellent model to study hearing loss as they have neurosensory hair cells on their body surface that are structurally similar to those within the human inner ear. Anatomic assays of toxin-mediated hair cell damage in zebrafish have been established; however, using fish swimming behavior - rheotaxis - as a biomarker for this anatomic damage was only recently described. We hypothesized that, in parallel, multilane measurements of rheotaxis could be used to create a high-throughput platform for drug development assessing both ototoxic and potentially otoprotective compounds in real time. Such a device was created, and results demonstrated a clear dose response between cisplatin exposure, progressive hair cell damage, and reduced rheotaxis in zebrafish. Furthermore, pre-exposure to the otoprotective medication dexamethasone, before cisplatin exposure, partially rescued rheotaxis swimming behavior and hair cell integrity. These results provide the first evidence that rescued swimming behavior can serve as a biomarker for rescued hair cell function. Developing a drug against hearing loss represents an unmet clinical need with global implications. Because hearing loss from diverse etiologies may result from common end-effects at the hair cell level, lessons learned from the present study may be broadly used.",
author = "Maki Niihori and Terry Platto and Suzu Igarashi and Audriana Hurbon and Dunn, {Allison M.} and Phi Tran and Hung Tran and Mudery, {Jordan A.} and Slepian, {Marvin J} and Abraham Jacob",
year = "2015",
month = "11",
day = "1",
doi = "10.1016/j.trsl.2015.05.002",
language = "English (US)",
volume = "166",
pages = "440--450",
journal = "Translational Research",
issn = "1931-5244",
publisher = "Mosby Inc.",
number = "5",

}

TY - JOUR

T1 - Zebrafish swimming behavior as a biomarker for ototoxicity-induced hair cell damage

T2 - A high-throughput drug development platform targeting hearing loss

AU - Niihori, Maki

AU - Platto, Terry

AU - Igarashi, Suzu

AU - Hurbon, Audriana

AU - Dunn, Allison M.

AU - Tran, Phi

AU - Tran, Hung

AU - Mudery, Jordan A.

AU - Slepian, Marvin J

AU - Jacob, Abraham

PY - 2015/11/1

Y1 - 2015/11/1

N2 - Hearing loss is one of the most common human sensory disabilities, adversely affecting communication, socialization, mood, physical functioning, and quality of life. In addition to age and noise-induced damage, ototoxicity is a common cause of sensorineural hearing loss with chemotherapeutic agents, for example, cisplatin, being a major contributor. Zebrafish (Danio rerio) are an excellent model to study hearing loss as they have neurosensory hair cells on their body surface that are structurally similar to those within the human inner ear. Anatomic assays of toxin-mediated hair cell damage in zebrafish have been established; however, using fish swimming behavior - rheotaxis - as a biomarker for this anatomic damage was only recently described. We hypothesized that, in parallel, multilane measurements of rheotaxis could be used to create a high-throughput platform for drug development assessing both ototoxic and potentially otoprotective compounds in real time. Such a device was created, and results demonstrated a clear dose response between cisplatin exposure, progressive hair cell damage, and reduced rheotaxis in zebrafish. Furthermore, pre-exposure to the otoprotective medication dexamethasone, before cisplatin exposure, partially rescued rheotaxis swimming behavior and hair cell integrity. These results provide the first evidence that rescued swimming behavior can serve as a biomarker for rescued hair cell function. Developing a drug against hearing loss represents an unmet clinical need with global implications. Because hearing loss from diverse etiologies may result from common end-effects at the hair cell level, lessons learned from the present study may be broadly used.

AB - Hearing loss is one of the most common human sensory disabilities, adversely affecting communication, socialization, mood, physical functioning, and quality of life. In addition to age and noise-induced damage, ototoxicity is a common cause of sensorineural hearing loss with chemotherapeutic agents, for example, cisplatin, being a major contributor. Zebrafish (Danio rerio) are an excellent model to study hearing loss as they have neurosensory hair cells on their body surface that are structurally similar to those within the human inner ear. Anatomic assays of toxin-mediated hair cell damage in zebrafish have been established; however, using fish swimming behavior - rheotaxis - as a biomarker for this anatomic damage was only recently described. We hypothesized that, in parallel, multilane measurements of rheotaxis could be used to create a high-throughput platform for drug development assessing both ototoxic and potentially otoprotective compounds in real time. Such a device was created, and results demonstrated a clear dose response between cisplatin exposure, progressive hair cell damage, and reduced rheotaxis in zebrafish. Furthermore, pre-exposure to the otoprotective medication dexamethasone, before cisplatin exposure, partially rescued rheotaxis swimming behavior and hair cell integrity. These results provide the first evidence that rescued swimming behavior can serve as a biomarker for rescued hair cell function. Developing a drug against hearing loss represents an unmet clinical need with global implications. Because hearing loss from diverse etiologies may result from common end-effects at the hair cell level, lessons learned from the present study may be broadly used.

UR - http://www.scopus.com/inward/record.url?scp=84944276681&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84944276681&partnerID=8YFLogxK

U2 - 10.1016/j.trsl.2015.05.002

DO - 10.1016/j.trsl.2015.05.002

M3 - Article

C2 - 26027789

AN - SCOPUS:84944276681

VL - 166

SP - 440

EP - 450

JO - Translational Research

JF - Translational Research

SN - 1931-5244

IS - 5

ER -