A gene cadre orchestrates the normal development of sensory and non-sensory cells in the inner ear, segregating the cochlea with a distinct tonotopic sound frequency map, similar brain projection, and five vestibular end-organs. However, the role of genes driving the ear development is largely unknown. Here, we show double deletion of the Iroquois homeobox 3 and 5 transcription factors (Irx3/5 DKO) leads to the fusion of the saccule and the cochlear base. The overlying otoconia and tectorial membranes are absent in the Irx3/5 DKO inner ear, and the primary auditory neurons project fibers to both the saccule and cochlear hair cells. The central neuronal projections from the cochlear apex-base contour are not fully segregated into a dorsal and ventral innervation in the Irx3/5 DKO cochlear nucleus, obliterating the characteristic tonotopic auditory map. Additionally, Irx3/5 deletion reveals a pronounced cochlear-apex-vestibular "vestibular-cochlear" nerve (VCN) bilateral connection that is less noticeable in wild-type control mice. Moreover, the incomplete segregation of apex and base projections that expands fibers to connect with vestibular nuclei. The results suggest the mammalian cochlear apex is a derived lagena reminiscent of sarcopterygians. Thus, Irx3 and 5 are potential evolutionary branch-point genes necessary for balance-sound segregation, which fused into a saccule-cochlea organization.
- MeSH
- homeodoménové proteiny * genetika metabolismus MeSH
- kochlea * fyziologie MeSH
- myši knockoutované * MeSH
- myši MeSH
- sakulus a utrikulus * fyziologie MeSH
- sluchová dráha fyziologie MeSH
- transkripční faktory * genetika metabolismus nedostatek MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Swept-sines provide a tool for fast and high-resolution measurement of evoked otoacoustic emissions. During the measurement, a response to swept-sine(s) is recorded by a probe placed in the ear canal. Otoacoustic emissions can then be extracted by various techniques, e.g., Fourier analysis, the heterodyne method, and the least-square-fitting (LSF) technique. This paper employs a technique originally proposed with exponential swept-sines, which allows for direct emission extraction from the measured intermodulation impulse response. It is shown here that the technique can be used to extract distortion-product otoacoustic emissions (DPOAEs) evoked with two simultaneous swept-sines. For proper extraction of the DPOAE phase, the technique employs previously proposed adjusted formulas for exponential swept-sines generating so-called synchronized swept-sines (SSSs). Here, the SSS technique is verified using responses derived from a numerical solution of a cochlear model and responses measured in human subjects. Although computationally much less demanding, the technique yields comparable results to those obtained by the LSF technique, which has been shown in the literature to be the most noise-robust among the emission extraction methods.
- MeSH
- Fourierova analýza MeSH
- kochlea * fyziologie MeSH
- lidé MeSH
- otoakustické emise spontánní * fyziologie MeSH
- zvukovod fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
INTRODUCTION: Currently, it is possible to preserve the auditory nerve in a large number of cases, but the preservation of the hearing itself is unpredictable. Apart from wait and scan strategy and stereoradiotherapy, hearing after vestibular schwannoma surgery is considered to remain stable even in long-term follow-up. MATERIALS AND METHODS: Twenty-eight patients had preserved hearing after retrosigmoid suboccipital microsurgery of the vestibular schwannoma between 2008 and 2014. A standard audiological protocol was performed together with an magnetic resonance imaging evaluation of the fluid content of the inner ear. RESULTS: The mean difference in pure-tone average between the direct and final postsurgical examination was 12.758 dB ( p = 2.5E - 06). The word recognition score deteriorated by 17.45% ( p = 0.03516). The mean American Academy of Otolaryngology-Head and Neck Surgery score on the second examination was 2.5, and that on the second examination was 3.111 ( p = 0.00483). There was no significant deterioration in the healthy ear.The signal intensity ratio in the basal turn of the cochlea increased by an average of 0.13 points ( p < 0.05).Patients with persistent tumor or nodular enhancement in the internal acoustic meatus deteriorated significantly in hearing according to the American Academy of Otolaryngology-Head and Neck Surgery scale compared with patients without any finding in the meatus ( p = 0.01299). CONCLUSIONS: There is a discrete but gradual deterioration of the hearing in the postoperative period. Hearing impairment is more pronounced in patients with a nodular process in the internal acoustic meatus, regardless of whether it is growth active. After surgery, the pathological content of the inner ear normalizes (evaluated on T2 magnetic resonance imaging sequences).
- MeSH
- kochlea MeSH
- lidé MeSH
- nedoslýchavost * etiologie MeSH
- retrospektivní studie MeSH
- sluch MeSH
- vestibulární schwannom * chirurgie MeSH
- vnitřní ucho * chirurgie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
V literatuře jsou dosud popsány řádově jednotky případů s vrozenou atrezií okrouhlého okénka. Podezření na diagnózu může vzniknout na základě předoperačního CT vyšetření, verifikace probíhá až během explorace středouší. Úplný uzávěr okrouhlého okénka způsobí velkou kostní rezervu a audiologický nález může připomínat otosklerózu. Prezentujeme případ 30leté ženy, která v minulosti prodělala 3 operace pro suspektní otosklerózu bez sluchového zisku. Během následné revize středouší byla zjištěna atrezie okrouhlého okénka a atypický tvar i abnormální pohyblivost ploténky. Pro funkčnost hydrodynamiky vnitřního ucha byla ještě provedena kochleární fenestrace. Přestože po operaci došlo k výraznému zlepšení kochleární rezervy na řečových frekvencích, pacientka subjektivně zlepšení sluchu nepozorovala. Ač se může předoperačně zdát otoskleróza být velmi pravděpodobnou příčinou poruchy sluchu, operatér by neměl opomenout zřídkavé, ale přesto se vyskytující raritní příčiny převodní nedoslýchavosti. Cílem tohoto sdělení je podělit se o poučení z provedených chyb, bez kterých by bylo možné předejít rizikům spojených s operací a umožnilo by lepší poučení pacientky před samotným zákrokem. Po každé stapedoplastice bez výrazného sluchového zisku by mělo být provedeno HR CT pyramid (k vyloučení syndromu třetího okénka nebo jiné zřídkavější abnormality), které by mohlo nasměrovat operatéra na méně častou etiologii potíží.
Only a few cases of a round windows atresia have been reported in the literature so far. The dia gnosis is based on the preoperative CT scan and local findings during a middle ear exploration. The complete round window closure leads to a significant conductive hearing loss. The hearing test result might be similar to the one found in otosclerosis. We report a case of 30-year-old woman, who previously underwent three surgeries for suspected otosclerosis without any hearing improvement. A round window atresia was only identified during following revision surgery, as well as a missing stapedial muscle, an abnormal shape and movement of the stapes footplate. In order to achieve a functional inner ear hydrodynamics, a cochlear fenestration was performed. Although there was a significant improvement in the cochlear reserve at speech frequencies after the operation, the patient didn’t report any hearing improvement. Although otosclerosis may be considered as a cause of the conductive hearing loss preoperatively, rare diagnoses should not be neglected. The aim of this case report is to share the experience and highlight mistakes made. After each unsuccessful stapedoplasty with unsatisfying hearing gain, a high resolution CT should be performed to exclude third window syndrome or another rare abnormality.
- Klíčová slova
- kochleární fenestrace, atrezie, stapedoplastika,
- MeSH
- dospělí MeSH
- fenestra rotunda * chirurgie patologie MeSH
- lidé MeSH
- otorinolaryngologické chirurgické výkony MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Different types of spiral ganglion neurons (SGNs) are essential for auditory perception by transmitting complex auditory information from hair cells (HCs) to the brain. Here, we use deep, single cell transcriptomics to study the molecular mechanisms that govern their identity and organization in mice. We identify a core set of temporally patterned genes and gene regulatory networks that may contribute to the diversification of SGNs through sequential binary decisions and demonstrate a role for NEUROD1 in driving specification of a Ic-SGN phenotype. We also find that each trajectory of the decision tree is defined by initial co-expression of alternative subtype molecular controls followed by gradual shifts toward cell fate resolution. Finally, analysis of both developing SGN and HC types reveals cell-cell signaling potentially playing a role in the differentiation of SGNs. Our results indicate that SGN identities are drafted prior to birth and reveal molecular principles that shape their differentiation and will facilitate studies of their development, physiology, and dysfunction.
- MeSH
- buněčná diferenciace genetika MeSH
- ganglion spirale * MeSH
- myši MeSH
- neurony * metabolismus MeSH
- RNA metabolismus MeSH
- vláskové buňky metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
We review the molecular basis of several transcription factors (Eya1, Sox2), including the three related genes coding basic helix-loop-helix (bHLH; see abbreviations) proteins (Neurog1, Neurod1, Atoh1) during the development of spiral ganglia, cochlear nuclei, and cochlear hair cells. Neuronal development requires Neurog1, followed by its downstream target Neurod1, to cross-regulate Atoh1 expression. In contrast, hair cells and cochlear nuclei critically depend on Atoh1 and require Neurod1 expression for interactions with Atoh1. Upregulation of Atoh1 following Neurod1 loss changes some vestibular neurons' fate into "hair cells", highlighting the significant interplay between the bHLH genes. Further work showed that replacing Atoh1 by Neurog1 rescues some hair cells from complete absence observed in Atoh1 null mutants, suggesting that bHLH genes can partially replace one another. The inhibition of Atoh1 by Neurod1 is essential for proper neuronal cell fate, and in the absence of Neurod1, Atoh1 is upregulated, resulting in the formation of "intraganglionic" HCs. Additional genes, such as Eya1/Six1, Sox2, Pax2, Gata3, Fgfr2b, Foxg1, and Lmx1a/b, play a role in the auditory system. Finally, both Lmx1a and Lmx1b genes are essential for the cochlear organ of Corti, spiral ganglion neuron, and cochlear nuclei formation. We integrate the mammalian auditory system development to provide comprehensive insights beyond the limited perception driven by singular investigations of cochlear neurons, cochlear hair cells, and cochlear nuclei. A detailed analysis of gene expression is needed to understand better how upstream regulators facilitate gene interactions and mammalian auditory system development.
- MeSH
- kochlea cytologie metabolismus MeSH
- lidé MeSH
- neurogeneze genetika fyziologie MeSH
- transkripční faktory bHLH genetika metabolismus MeSH
- transkripční faktory genetika metabolismus MeSH
- vláskové buňky metabolismus MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
This review provides an up-to-date source of information on the primary auditory neurons or spiral ganglion neurons in the cochlea. These neurons transmit auditory information in the form of electric signals from sensory hair cells to the first auditory nuclei of the brain stem, the cochlear nuclei. Congenital and acquired neurosensory hearing loss affects millions of people worldwide. An increasing body of evidence suggest that the primary auditory neurons degenerate due to noise exposure and aging more readily than sensory cells, and thus, auditory neurons are a primary target for regenerative therapy. A better understanding of the development and function of these neurons is the ultimate goal for long-term maintenance, regeneration, and stem cell replacement therapy. In this review, we provide an overview of the key molecular factors responsible for the function and neurogenesis of the primary auditory neurons, as well as a brief introduction to stem cell research focused on the replacement and generation of auditory neurons.
- MeSH
- ganglion spirale embryologie fyziologie MeSH
- indukované pluripotentní kmenové buňky cytologie MeSH
- kochlea embryologie fyziologie MeSH
- lidé MeSH
- mozkový kmen MeSH
- mutace MeSH
- myši MeSH
- neurogeneze MeSH
- neurony fyziologie MeSH
- nucleus cochlearis embryologie fyziologie MeSH
- percepční nedoslýchavost patofyziologie MeSH
- regenerativní lékařství metody MeSH
- sekvence nukleotidů MeSH
- sluchové kmenové evokované potenciály MeSH
- vláskové buňky fyziologie MeSH
- vnitřní ucho embryologie fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
To examine whether exposure to sodium salicylate disrupts expression of vesicular glutamate transporter 3 (VGLUT3) and whether the alteration in expression corresponds to increased risk for tinnitus. Rats were treated with saline (control) or sodium salicylate (treated) Rats were examined for tinnitus by monitoring gap-pre-pulse inhibition of the acoustic startle reflex (GPIAS). Auditory brainstem response (ABR) was applied to evaluate hearing function after treatment. Rats were sacrificed after injection to obtain the cochlea, cochlear nucleus (CN), and inferior colliculus (IC) for examination of VGLUT3 expression. No significant differences in hearing thresholds between groups were identified (p>0.05). Tinnitus in sodium salicylate-treated rats was confirmed by GPIAS. VGLUT3 encoded by solute carrier family 17 members 8 (SLC17a8) expression was significantly increased in inner hair cells (IHCs) of the cochlea in treated animals, compared with controls (p<0.01). No significant differences in VGLUT3 expression between groups were found for the cochlear nucleus (CN) or IC (p>0.05). Exposure to sodium salicylate may disrupt SLC17a8 expression in IHCs, leading to alterations that correspond to tinnitus in rats. However, the CN and IC are unaffected by exposure to sodium salicylate, suggesting that enhancement of VGLUT3 expression in IHCs may contribute to the pathogenesis of tinnitus.
- MeSH
- antiflogistika nesteroidní škodlivé účinky MeSH
- colliculus inferior účinky léků metabolismus MeSH
- nucleus cochlearis účinky léků metabolismus MeSH
- potkani Wistar MeSH
- salicylan sodný škodlivé účinky MeSH
- sluchový práh účinky léků MeSH
- tinnitus chemicky indukované MeSH
- vezikulární transportní proteiny pro glutamát metabolismus MeSH
- vnitřní vláskové buňky účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Sensorineural hearing loss and vertigo, resulting from lesions in the sensory epithelium of the inner ear, have a high incidence worldwide. The sensory epithelium of the inner ear may exhibit extreme degeneration and is transformed to flat epithelium (FE) in humans and mice with profound sensorineural hearing loss and/or vertigo. Various factors, including ototoxic drugs, noise exposure, aging, and genetic defects, can induce FE. Both hair cells and supporting cells are severely damaged in FE, and the normal cytoarchitecture of the sensory epithelium is replaced by a monolayer of very thin, flat cells of irregular contour. The pathophysiologic mechanism of FE is unclear but involves robust cell division. The cellular origin of flat cells in FE is heterogeneous; they may be transformed from supporting cells that have lost some features of supporting cells (dedifferentiation) or may have migrated from the flanking region. The epithelial-mesenchymal transition may play an important role in this process. The treatment of FE is challenging given the severe degeneration and loss of both hair cells and supporting cells. Cochlear implant or vestibular prosthesis implantation, gene therapy, and stem cell therapy show promise for the treatment of FE, although many challenges remain to be overcome.
- MeSH
- epitel zranění patologie MeSH
- epitelo-mezenchymální tranzice MeSH
- hluk škodlivé účinky MeSH
- lidé MeSH
- percepční nedoslýchavost metabolismus patologie MeSH
- vnitřní ucho zranění metabolismus patologie MeSH
- vnitřní vláskové buňky metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
