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Molecular mechanisms in the development of the cochlea
Procházková, Šárka ; Pavlínková, Gabriela (advisor) ; Novák, Josef (referee)
Molecular mechanisms in the development of the cochlea The cochlea is the primary structure for the perception of sound. A spiraled cochlear duct contains the auditory organ, the organ of Corti, is innervated by sensory neurons of the spiral ganglion. The organ of Corti contains hair cells, the sensory receptors of the inner ear, that are responsible for the mechano-transduction of sound waves into electrical signals. The development of the cochlea is regulated by the cellular and molecular processes, including cochlear outgrowth, cellular differentiation, and patterning. The precise coordination of multiple processes during the transformation of a flat embryonic epithelium into the cellular mosaic of the adult structure requires a multitude of transcription factors and signaling pathways. These regulatory networks dictate cell fate and timing decisions during cochlear development. Interestingly, these mechanisms operate as well during sensory epithelial cell regeneration after damage and during stem cell directed differentiation, making developmental studies instrumental for improving therapies for hearing impairment.
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Role of Islet1, BDNF and nanoparticles in development, function and regeneration of the auditory system
Chumak, Tetyana ; Syka, Josef (advisor) ; Druga, Rastislav (referee) ; Maršálek, Petr (referee)
Detailed knowledge of the role that particular genes and factors play during the development and in the normal function of the auditory system is necessary to develop successful regenerative inner ear therapies. Islet1 transcription factor and brain derived neurothrophic factor (BDNF) have great potential to play a role in regenerative inner ear therapy as both have been shown to be sufficient for self-repair regeneration in cochlea in animal studies. In this study we looked at the roles these two factors play in the development and function of the auditory system. In the transgenic mice used in the study, overexpression of Isl1 affected cell specification during embryonic development, leading to enlargement of the cochleovestibular ganglion and accelerated nerve fiber extension and branching in mutant embryos. The hearing of young transgenic mice was not affected. However, it started to decline in 1-month-old animals. This early onset of age-related hearing loss was found to be a consequence of the neurodegeneration of the olivocochlear system caused by Pax2-driven Isl1 misexpression in the hindbrain. Our data provide the first evidence that the alternation of the olivocochlear system efferent system accelerates the age-related functional decline of hearing without the loss of OHCs. The functional role of...
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Computer modeling of the inner ear
Perlácová, Tereza ; Jungwirth, Pavel (advisor) ; Vejchodský, Tomáš (referee)
Do mechanického modelu kochley zavádzame implicitné numerické metódy. Tes- tujeme konkrétne štyri metódy: implicitný Euler, Crank-Nicolson, BDF druhého a tretieho rádu na lineárnej a nelineárnej verzii modelu. Nelineárny model obsahuje funkciu so saturujúcou vlastnosťou. Aplikácia implicitných metód na nelineárny model vedie na sústavu nelineárnych rovníc. Predstavujeme dva spôsoby, ako túto sústavu numericky riešiť. Prvý z nich zahrňuje nelinearitu do pravej strany novovzniknutej lineárnej sústavy. Druhý robí linearizáciu nelineárnej funkcie. V práci porovnávame oba spôsoby z hľadiska efektivity a sledujeme ich konvergenciu k referenčnému riešeniu. Pre hodnotu tolerancie, ktorú používame na určenie numerickej konvergencie, je prvý spôsob efektívnejší. V úplne nelineárnom režime druhý spôsob zlyháva, pretože nekon- verguje k referenčnému riešeniu. Výsledkom porovnania implicitných metód je, že Crank-Nicolsonova metóda s prvým spôsobom riešenia nelineárnej sústavy je pre účely nášho modelu najlepšia. Použitie tejto metódy v mechanickom modeli nám umožňuje vytvoriť ľubovoľne presné prepojenie medzi mechanickým a elektrickým modelom kochley, rešpektujúc fyziológiu človeka. 1
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Role of Islet1, BDNF and nanoparticles in development, function and regeneration of the auditory system
Chumak, Tetyana ; Syka, Josef (advisor) ; Druga, Rastislav (referee) ; Maršálek, Petr (referee)
Detailed knowledge of the role that particular genes and factors play during the development and in the normal function of the auditory system is necessary to develop successful regenerative inner ear therapies. Islet1 transcription factor and brain derived neurothrophic factor (BDNF) have great potential to play a role in regenerative inner ear therapy as both have been shown to be sufficient for self-repair regeneration in cochlea in animal studies. In this study we looked at the roles these two factors play in the development and function of the auditory system. In the transgenic mice used in the study, overexpression of Isl1 affected cell specification during embryonic development, leading to enlargement of the cochleovestibular ganglion and accelerated nerve fiber extension and branching in mutant embryos. The hearing of young transgenic mice was not affected. However, it started to decline in 1-month-old animals. This early onset of age-related hearing loss was found to be a consequence of the neurodegeneration of the olivocochlear system caused by Pax2-driven Isl1 misexpression in the hindbrain. Our data provide the first evidence that the alternation of the olivocochlear system efferent system accelerates the age-related functional decline of hearing without the loss of OHCs. The functional role of...
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