Deterioration of the Medial Olivocochlear Efferent System Accelerates Age-Related Hearing Loss in Pax2-Isl1 Transgenic Mice

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F16%3A00454012" target="_blank" >RIV/86652036:_____/16:00454012 - isvavai.cz</a>

Alternative codes found

RIV/68378041:_____/16:00454012

Result on the web

<a href="http://dx.doi.org/10.1007/s12035-015-9215-1" target="_blank" >http://dx.doi.org/10.1007/s12035-015-9215-1</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s12035-015-9215-1" target="_blank" >10.1007/s12035-015-9215-1</a>

Result language

angličtina

Original language name

Deterioration of the Medial Olivocochlear Efferent System Accelerates Age-Related Hearing Loss in Pax2-Isl1 Transgenic Mice

Original language description

The development, maturation, and maintenance of the inner ear are governed by temporal and spatial expression cascades of transcription factors that form a gene regulatory network. ISLET1 (ISL1) may be one of the major players in this cascade, and in order to study its role in the regulation of inner ear development, we produced a transgenic mouse overexpressing Isl1 under the Pax2 promoter. Pax2-regulated ISL1 overexpression increases the embryonic ISL1+ domain and induces accelerated nerve fiber extension and branching in E12.5 embryos. Despite these gains in early development, the overexpression of ISL1 impairs the maintenance and function of hair cells of the organ of Corti. Mutant mice exhibit hyperactivity, circling behavior, and progressive age-related decline in hearing functions, which is reflected in reduced otoacoustic emissions (DPOAEs) followed by elevated hearing thresholds. The reduction of the amplitude of DPOAEs in transgenic mice was first detected at 1 month of age. By 6-9 months of age, DPOAEs completely disappeared, suggesting a functional inefficiency of outer hair cells (OHCs). The timing of DPOAE reduction coincides with the onset of the deterioration of cochlear efferent terminals. In contrast to these effects on efferents, we only found a moderate loss of OHCs and spiral ganglion neurons. For the first time, our results show that the genetic alteration of the medial olivocochlear (MOC) efferent system induces an early onset of age-related hearing loss. Thus, the neurodegeneration of the MOC system could be a contributing factor to the pathology of age-related hearing loss.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Molecular Neurobiology

ISSN

0893-7648

e-ISSN

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Volume of the periodical

53

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

16

Pages from-to

2368-2383

UT code for WoS article

000373641500027

EID of the result in the Scopus database

2-s2.0-84929689126