Regeneration of Cochlear Synapses by Systemic Administration of a Bisphosphonate

Sensorineural hearing loss (SNHL) caused by noise exposure and attendant loss of glutamatergic synapses between cochlear spiral ganglion neurons (SGNs) and hair cells is the most common sensory deficit worldwide. We show here that systemic administration of a bisphosphonate to mice 24 h after synapt...

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Autores principales: Seist, Richard, Tong, Mingjie, Landegger, Lukas D., Vasilijic, Sasa, Hyakusoku, Hiroshi, Katsumi, Sachiyo, McKenna, Charles E., Edge, Albert S. B., Stankovic, Konstantina M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Neuroscience
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381223/
https://www.ncbi.nlm.nih.gov/pubmed/32765216
http://dx.doi.org/10.3389/fnmol.2020.00087
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author Seist, Richard
Tong, Mingjie
Landegger, Lukas D.
Vasilijic, Sasa
Hyakusoku, Hiroshi
Katsumi, Sachiyo
McKenna, Charles E.
Edge, Albert S. B.
Stankovic, Konstantina M.
author_facet Seist, Richard
Tong, Mingjie
Landegger, Lukas D.
Vasilijic, Sasa
Hyakusoku, Hiroshi
Katsumi, Sachiyo
McKenna, Charles E.
Edge, Albert S. B.
Stankovic, Konstantina M.
author_sort Seist, Richard
collection PubMed
description Sensorineural hearing loss (SNHL) caused by noise exposure and attendant loss of glutamatergic synapses between cochlear spiral ganglion neurons (SGNs) and hair cells is the most common sensory deficit worldwide. We show here that systemic administration of a bisphosphonate to mice 24 h after synaptopathic noise exposure regenerated synapses between inner hair cells and SGNs and restored cochlear function. We further demonstrate that this effect is mediated by inhibition of the mevalonate pathway. These results are highly significant because they suggest that bisphosphonates could reverse cochlear synaptopathy for the treatment of SNHL.
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spelling pubmed-73812232020-08-05 Regeneration of Cochlear Synapses by Systemic Administration of a Bisphosphonate Seist, Richard Tong, Mingjie Landegger, Lukas D. Vasilijic, Sasa Hyakusoku, Hiroshi Katsumi, Sachiyo McKenna, Charles E. Edge, Albert S. B. Stankovic, Konstantina M. Front Mol Neurosci Neuroscience Sensorineural hearing loss (SNHL) caused by noise exposure and attendant loss of glutamatergic synapses between cochlear spiral ganglion neurons (SGNs) and hair cells is the most common sensory deficit worldwide. We show here that systemic administration of a bisphosphonate to mice 24 h after synaptopathic noise exposure regenerated synapses between inner hair cells and SGNs and restored cochlear function. We further demonstrate that this effect is mediated by inhibition of the mevalonate pathway. These results are highly significant because they suggest that bisphosphonates could reverse cochlear synaptopathy for the treatment of SNHL. Frontiers Media S.A. 2020-07-14 /pmc/articles/PMC7381223/ /pubmed/32765216 http://dx.doi.org/10.3389/fnmol.2020.00087 Text en Copyright © 2020 Seist, Tong, Landegger, Vasilijic, Hyakusoku, Katsumi, McKenna, Edge and Stankovic. http://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 Neuroscience
Seist, Richard
Tong, Mingjie
Landegger, Lukas D.
Vasilijic, Sasa
Hyakusoku, Hiroshi
Katsumi, Sachiyo
McKenna, Charles E.
Edge, Albert S. B.
Stankovic, Konstantina M.
Regeneration of Cochlear Synapses by Systemic Administration of a Bisphosphonate
title Regeneration of Cochlear Synapses by Systemic Administration of a Bisphosphonate
title_full Regeneration of Cochlear Synapses by Systemic Administration of a Bisphosphonate
title_fullStr Regeneration of Cochlear Synapses by Systemic Administration of a Bisphosphonate
title_full_unstemmed Regeneration of Cochlear Synapses by Systemic Administration of a Bisphosphonate
title_short Regeneration of Cochlear Synapses by Systemic Administration of a Bisphosphonate
title_sort regeneration of cochlear synapses by systemic administration of a bisphosphonate
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381223/
https://www.ncbi.nlm.nih.gov/pubmed/32765216
http://dx.doi.org/10.3389/fnmol.2020.00087
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