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Research
Kunio Mizutari
National Defense Medical College: Boei Ika Daigakko
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0340-8293
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Recently, a pathological condition called cochlear synaptopathy has been clarified, and as a disorder of the auditory nerve synapses that occurs prior to failure of hair cells it has been recognized as a major cause of sensorineural hearing loss. However, cochlear synaptopathy is untreatable. Inhibition of rho-associated coiled-coil containing protein kinase (ROCK), a serine-threonine protein kinase, has been reported to have neuroprotective and regenerative effects on synaptic pathways in the nervous system, including those in the inner ear. We previously demonstrated the regenerative effect of the ROCK inhibitor, Y-27632, on an excitotoxic cochlear nerve damage model in vitro. In this study, we aimed to validate the effect of ROCK inhibition on mice with cochlear synaptopathy induced by laser-induced shock wave (LISW) in vivo. After the elevation of ROCK1/2 expression in the damaged cochlea was confirmed, we administered Y-27632 locally via the middle ear. The amplitude of wave I in the auditory brainstem response and the number of synapses in the Y-27632-treated cochlea increased significantly. These results clearly demonstrate that ROCK inhibition has a promising clinical application in the treatment of cochlear synaptopathy, which is the major pathology of sensorineural hearing loss.
Keywords
Cochlea, Rho-associated coiled-coil containing protein kinase (ROCK), synapse, regeneration, Y-27632, hearing loss, inner ear
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CURRENT STATUS: Under Review
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Posted 13 Apr, 2021
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Editorial decision: Major revision
On 31 May, 2021
Review #3 received
Received 07 May, 2021
Review #2 received
Received 07 May, 2021
Reviewer #3 agreed
On 04 May, 2021
Reviewer #2 agreed
On 04 May, 2021
Review #1 received
Received 15 Apr, 2021
Reviewer #1 agreed
On 10 Apr, 2021
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Invitations sent on 10 Apr, 2021
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On 07 Apr, 2021
Submission checks complete
On 07 Apr, 2021
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On 07 Apr, 2021
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On 06 Apr, 2021
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Subject Areas
Cellular & Molecular Neuroscience
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This preprint is under consideration at Molecular Brain. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Kunio Mizutari
National Defense Medical College: Boei Ika Daigakko
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0340-8293
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 13 Apr, 2021
No community comments so far
Editorial decision: Major revision
On 31 May, 2021
Review #3 received
Received 07 May, 2021
Review #2 received
Received 07 May, 2021
Reviewer #3 agreed
On 04 May, 2021
Reviewer #2 agreed
On 04 May, 2021
Review #1 received
Received 15 Apr, 2021
Reviewer #1 agreed
On 10 Apr, 2021
Reviewers invited
Invitations sent on 10 Apr, 2021
Editor assigned
On 07 Apr, 2021
Submission checks complete
On 07 Apr, 2021
Editor invited
On 07 Apr, 2021
First submitted
On 06 Apr, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cellular & Molecular Neuroscience
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Recently, a pathological condition called cochlear synaptopathy has been clarified, and as a disorder of the auditory nerve synapses that occurs prior to failure of hair cells it has been recognized as a major cause of sensorineural hearing loss. However, cochlear synaptopathy is untreatable. Inhibition of rho-associated coiled-coil containing protein kinase (ROCK), a serine-threonine protein kinase, has been reported to have neuroprotective and regenerative effects on synaptic pathways in the nervous system, including those in the inner ear. We previously demonstrated the regenerative effect of the ROCK inhibitor, Y-27632, on an excitotoxic cochlear nerve damage model in vitro. In this study, we aimed to validate the effect of ROCK inhibition on mice with cochlear synaptopathy induced by laser-induced shock wave (LISW) in vivo. After the elevation of ROCK1/2 expression in the damaged cochlea was confirmed, we administered Y-27632 locally via the middle ear. The amplitude of wave I in the auditory brainstem response and the number of synapses in the Y-27632-treated cochlea increased significantly. These results clearly demonstrate that ROCK inhibition has a promising clinical application in the treatment of cochlear synaptopathy, which is the major pathology of sensorineural hearing loss.
Figure 1
Figure 2
Figure 3
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