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Reactivation of the Neurogenic Niche in the Adult Zebrafish Statoacoustic Ganglion Following a Mechanical Lesion

Sensorineural hearing loss is caused by the loss of sensory hair cells and/or their innervating neurons within the inner ear and affects millions of people worldwide. In mammals, including humans, the underlying cell types are only produced during fetal stages making loss of these cells and the resu...

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Autores principales: Schwarzer, Simone, Rekhade, Devavrat Ravindra, Machate, Anja, Spieß, Sandra, Geffarth, Michaela, Ezhkova, Diana, Hans, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964994/
https://www.ncbi.nlm.nih.gov/pubmed/35372332
http://dx.doi.org/10.3389/fcell.2022.850624
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author Schwarzer, Simone
Rekhade, Devavrat Ravindra
Machate, Anja
Spieß, Sandra
Geffarth, Michaela
Ezhkova, Diana
Hans, Stefan
author_facet Schwarzer, Simone
Rekhade, Devavrat Ravindra
Machate, Anja
Spieß, Sandra
Geffarth, Michaela
Ezhkova, Diana
Hans, Stefan
author_sort Schwarzer, Simone
collection PubMed
description Sensorineural hearing loss is caused by the loss of sensory hair cells and/or their innervating neurons within the inner ear and affects millions of people worldwide. In mammals, including humans, the underlying cell types are only produced during fetal stages making loss of these cells and the resulting consequences irreversible. In contrast, zebrafish produce sensory hair cells throughout life and additionally possess the remarkable capacity to regenerate them upon lesion. Recently, we showed that also inner ear neurogenesis continues to take place in the zebrafish statoacoustic ganglion (SAG) well into adulthood. The neurogenic niche displays presumptive stem cells, proliferating Neurod-positive progenitors and a high level of neurogenesis at juvenile stages. It turns dormant at adult stages with only a few proliferating presumptive stem cells, no proliferating Neurod-positive progenitors, and very low levels of newborn neurons. Whether the neurogenic niche can be reactivated and whether SAG neurons can regenerate upon damage is unknown. To study the regenerative capacity of the SAG, we established a lesion paradigm using injections into the otic capsule of the right ear. Upon lesion, the number of apoptotic cells increased, and immune cells infiltrated the SAG of the lesioned side. Importantly, the Neurod-positive progenitor cells re-entered the cell cycle displaying a peak in proliferation at 8 days post lesion before they returned to homeostatic levels at 57 days post lesion. In parallel to reactive proliferation, we observed increased neurogenesis from the Neurod-positive progenitor pool. Reactive neurogenesis started at around 4 days post lesion peaking at 8 days post lesion before the neurogenesis rate decreased again to low homeostatic levels at 57 days post lesion. Additionally, administration of the thymidine analog BrdU and, thereby, labeling proliferating cells and their progeny revealed the generation of new sensory neurons within 19 days post lesion. Taken together, we show that the neurogenic niche of the adult zebrafish SAG can indeed be reactivated to re-enter the cell cycle and to increase neurogenesis upon lesion. Studying the underlying genes and pathways in zebrafish will allow comparative studies with mammalian species and might provide valuable insights into developing cures for auditory and vestibular neuropathies.
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spelling pubmed-89649942022-03-31 Reactivation of the Neurogenic Niche in the Adult Zebrafish Statoacoustic Ganglion Following a Mechanical Lesion Schwarzer, Simone Rekhade, Devavrat Ravindra Machate, Anja Spieß, Sandra Geffarth, Michaela Ezhkova, Diana Hans, Stefan Front Cell Dev Biol Cell and Developmental Biology Sensorineural hearing loss is caused by the loss of sensory hair cells and/or their innervating neurons within the inner ear and affects millions of people worldwide. In mammals, including humans, the underlying cell types are only produced during fetal stages making loss of these cells and the resulting consequences irreversible. In contrast, zebrafish produce sensory hair cells throughout life and additionally possess the remarkable capacity to regenerate them upon lesion. Recently, we showed that also inner ear neurogenesis continues to take place in the zebrafish statoacoustic ganglion (SAG) well into adulthood. The neurogenic niche displays presumptive stem cells, proliferating Neurod-positive progenitors and a high level of neurogenesis at juvenile stages. It turns dormant at adult stages with only a few proliferating presumptive stem cells, no proliferating Neurod-positive progenitors, and very low levels of newborn neurons. Whether the neurogenic niche can be reactivated and whether SAG neurons can regenerate upon damage is unknown. To study the regenerative capacity of the SAG, we established a lesion paradigm using injections into the otic capsule of the right ear. Upon lesion, the number of apoptotic cells increased, and immune cells infiltrated the SAG of the lesioned side. Importantly, the Neurod-positive progenitor cells re-entered the cell cycle displaying a peak in proliferation at 8 days post lesion before they returned to homeostatic levels at 57 days post lesion. In parallel to reactive proliferation, we observed increased neurogenesis from the Neurod-positive progenitor pool. Reactive neurogenesis started at around 4 days post lesion peaking at 8 days post lesion before the neurogenesis rate decreased again to low homeostatic levels at 57 days post lesion. Additionally, administration of the thymidine analog BrdU and, thereby, labeling proliferating cells and their progeny revealed the generation of new sensory neurons within 19 days post lesion. Taken together, we show that the neurogenic niche of the adult zebrafish SAG can indeed be reactivated to re-enter the cell cycle and to increase neurogenesis upon lesion. Studying the underlying genes and pathways in zebrafish will allow comparative studies with mammalian species and might provide valuable insights into developing cures for auditory and vestibular neuropathies. Frontiers Media S.A. 2022-03-15 /pmc/articles/PMC8964994/ /pubmed/35372332 http://dx.doi.org/10.3389/fcell.2022.850624 Text en Copyright © 2022 Schwarzer, Rekhade, Machate, Spieß, Geffarth, Ezhkova and Hans. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Schwarzer, Simone
Rekhade, Devavrat Ravindra
Machate, Anja
Spieß, Sandra
Geffarth, Michaela
Ezhkova, Diana
Hans, Stefan
Reactivation of the Neurogenic Niche in the Adult Zebrafish Statoacoustic Ganglion Following a Mechanical Lesion
title Reactivation of the Neurogenic Niche in the Adult Zebrafish Statoacoustic Ganglion Following a Mechanical Lesion
title_full Reactivation of the Neurogenic Niche in the Adult Zebrafish Statoacoustic Ganglion Following a Mechanical Lesion
title_fullStr Reactivation of the Neurogenic Niche in the Adult Zebrafish Statoacoustic Ganglion Following a Mechanical Lesion
title_full_unstemmed Reactivation of the Neurogenic Niche in the Adult Zebrafish Statoacoustic Ganglion Following a Mechanical Lesion
title_short Reactivation of the Neurogenic Niche in the Adult Zebrafish Statoacoustic Ganglion Following a Mechanical Lesion
title_sort reactivation of the neurogenic niche in the adult zebrafish statoacoustic ganglion following a mechanical lesion
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964994/
https://www.ncbi.nlm.nih.gov/pubmed/35372332
http://dx.doi.org/10.3389/fcell.2022.850624
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