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A Protective Role for Type 3 Deiodinase, a Thyroid Hormone-Inactivating Enzyme, in Cochlear Development and Auditory Function

Ng, Lily; Hernandez, Arturo; He, Wenxuan; Ren, Tianying; Srinivas, Maya; Ma, Michelle; Galton, Valerie A.; St. Germain, Donald L.; Forrest, Douglas
Fonte: The Endocrine Society Publicador: The Endocrine Society
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
17.425059%
Thyroid hormone is necessary for cochlear development and auditory function, but the factors that control these processes are poorly understood. Previous evidence indicated that in mice, the serum supply of thyroid hormone is augmented within the cochlea itself by type 2 deiodinase, which amplifies the level of T3, the active form of thyroid hormone, before the onset of hearing. We now report that type 3 deiodinase, a thyroid hormone-inactivating enzyme encoded by Dio3, is expressed in the immature cochlea before type 2 deiodinase. Dio3−/− mice display auditory deficits and accelerated cochlear differentiation, contrasting with the retardation caused by deletion of type 2 deiodinase. The Dio3 mRNA expression pattern in the greater epithelial ridge, stria vascularis, and spiral ganglion partly overlaps with that of thyroid hormone receptor β (TRβ), the T3 receptor that is primarily responsible for auditory development. The proposal that type 3 deiodinase prevents premature stimulation of TRβ was supported by deleting TRβ, which converted the Dio3−/− cochlear phenotype from one of accelerated to one of delayed differentiation. The results indicate a protective role for type 3 deiodinase in hearing. The auditory system illustrates the considerable extent to which tissues can autoregulate their developmental response to thyroid hormone through both type 2 and 3 deiodinases.

The effect of tectorial membrane and basilar membrane longitudinal coupling in cochlear mechanics

Meaud, Julien; Grosh, Karl
Fonte: Acoustical Society of America Publicador: Acoustical Society of America
Tipo: Artigo de Revista Científica
Publicado em /03/2010 EN
Relevância na Pesquisa
17.660829%
Most mathematical models of the mammalian cochlea neglect structural longitudinal coupling. However, recent experimental data suggest that viscoelastic longitudinal coupling, in the basilar membrane (BM) and the tectorial membrane (TM), is non-negligible. In this paper, mathematical models for BM and TM longitudinal coupling are presented to determine the influence of such a coupling on the tuning of the BM. The longitudinal coupling models are added to a macroscopic linear model of the guinea pig cochlea that includes the micromechanics of the organ of Corti and outer hair cell (OHC) somatic motility. The predictions of the BM response to acoustic stimulus show that the characteristic frequency is controlled by a TM radial resonance and that TM longitudinal coupling has a more significant effect than BM longitudinal coupling. TM viscoelasticity controls the sharpness of the BM frequency response and the duration of the impulse response. The results with realistic TM longitudinal coupling are more consistent with experiments. The model predicts that OHC somatic electromotility is able to supply power to the BM at frequencies well above the cutoff of the OHC basolateral membrane. Moreover, TM longitudinal coupling is predicted to stabilize the cochlea and enable a higher BM sensitivity to acoustic stimulation.

Spiral ganglion neuron survival and function in the deafened cochlea following chronic neurotrophic treatment

Landry, Thomas G.; Wise, Andrew K.; Fallon, James B.; Shepherd, Robert K.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
27.425059%
Cochlear implants electrically stimulate residual spiral ganglion neurons (SGNs) to provide auditory cues for the severe-profoundly deaf. However, SGNs gradually degenerate following cochlear hair cell loss, leaving fewer neurons available for stimulation. Providing an exogenous supply of neurotrophins (NTs) has been shown to prevent SGN degeneration, and when combined with chronic intracochlear electrical stimulation (ES) following a short period of deafness (5 days), may also promote the formation of new neurons. The present study assessed the histopathological response of guinea pig cochleae treated with NTs (brain-derived neurotrophic factor and neurotrophin-3) with and without ES over a four week period, initiated two-weeks after deafening. Results were compared to both NT alone and artificial perilymph (AP) treated animals. AP/ES treated animals exhibited no evidence of SGN rescue compared with untreated deafened controls. In contrast, NT administration showed a significant SGN rescue effect in the lower and middle cochlear turns (two-way ANOVA, p < 0.05) compared with AP-treated control animals. ES in combination with NT did not enhance SGN survival compared with NT alone. SGN function was assessed by measuring electrically-evoked auditory brainstem response (EABR) thresholds. EABR thresholds following NT treatment were significantly lower than animals treated with AP (two-way ANOVA...

Otoferlin couples to clathrin-mediated endocytosis in mature cochlear inner hair cells

Duncker, Susanne V.; Franz, Christoph; Kuhn, Stephanie; Schulte, Uwe; Campanelli, Dario; Brandt, Niels; Hirt, Bernhard; Fakler, Bernd; Blin, Nikolaus; Ruth, Peter; Engel, Jutta; Marcotti, Walter; Zimmermann, Ulrike; Knipper, Marlies
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 29/05/2013 EN
Relevância na Pesquisa
16.974955%
The encoding of auditory information with indefatigable precision requires efficient re-supply of vesicles at inner hair cell (IHC) ribbon synapses. Otoferlin, a transmembrane protein responsible for deafness in DFNB9 families, has been postulated to act as a calcium sensor for exocytosis as well as to be involved in rapid vesicle replenishment of IHCs. However, the molecular basis of vesicle recycling in IHCs is largely unknown. In the present study, we used high-resolution liquid chromatography coupled with mass spectrometry to co-purify otoferlin interaction partners in the mammalian cochlea. We identified multiple subunits of the adaptor protein complex AP-2 (CLAP), an essential component of clathrin-mediated endocytosis, as binding partners of otoferlin in rats and mice. The interaction between otoferlin and AP-2 was confirmed by co-immunoprecipitation. We also found that AP-2 interacts with myosin VI, another otoferlin binding partner important for clathrin-mediated endocytosis. The expression of AP-2 in IHCs was verified by RT-PCR. Confocal microscopy experiments revealed that the expression of AP-2 and its co-localization with otoferlin is confined to mature IHCs. When clathrin-mediated endocytosis was inhibited by blocking dynamin action...

Chronic Neurotrophin Delivery Promotes Ectopic Neurite Growth From the Spiral Ganglion of Deafened Cochleae Without Compromising the Spatial Selectivity of Cochlear Implants

Landry, Thomas G.; Fallon, James B.; Wise, Andrew K.; Shepherd, Robert K.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/08/2013 EN
Relevância na Pesquisa
17.425059%
Cochlear implants restore hearing cues in the severe– profoundly deaf by electrically stimulating spiral ganglion neurons (SGNs). However, SGNs degenerate following loss of cochlear hair cells, due at least in part to a reduction in the endogenous neurotrophin (NT) supply, normally provided by hair cells and supporting cells of the organ of Corti. Delivering exogenous NTs to the cochlea can rescue SGNs from degeneration and can also promote the ectopic growth of SGN neurites. This resprouting may disrupt the cochleotopic organization upon which cochlear implants rely to impart pitch cues. Using retrograde labeling and confocal imaging of SGNs, we determined the extent of neurite growth following 28 days of exogenous NT treatment in deafened guinea pigs with and without chronic electrical stimulation (ES). On completion of this treatment, we measured the spread of neural activation to intracochlear ES by recording neural responses across the cochleotopically organized inferior colliculus using multichannel recording techniques. Although NT treatment significantly increased both the length and the lateral extent of growth of neurites along the cochlea compared with deafened controls, these anatomical changes did not affect the spread of neural activation when examined immediately after 28 days of NT treatment. NT treatment did...

A low-power cochlear implant system

Baker, Michael W. (Michael Warren), 1977-
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 179 p.
ENG
Relevância na Pesquisa
16.974955%
Cochlear implants, or bionic ears, restore hearing to the profoundly deaf by bypassing missing inner-ear hair cells in the cochlea and electrically stimulating the auditory nerve. For miniaturized cochlear implants, including behind-the-ear (BTE) models, power consumption is the chief factor in determining cost and patient convenience. This thesis reports on the design of a low-power bionic ear system by addressing three critical signal and power processing subsystems in low-cost CMOS ICs. First, the design of a low-power current-mode front-end for subminiature microphones demonstrates 78dB dynamic range performance with attention to RF noise and supply immunity. Second, hearing-impaired patients need strategies that decide intelligently between listening conditions in speech or noise. This work describes an automatic gain control (AGC) design which uses programmable hybrid analog-digital current-mode feedback to implement a dual-loop strategy, a well-known algorithm for speech in noisy environments. The AGC exhibits level-invariant. stability, programmable time constants and consumes less than 36pW. Third, a feedback-loop technique is explored for analyzing and designing RF power links for transcutaneous bionic ear systems.; (cont.) Using feedback tools to minimize algebraic manipulations...

Modeling and design of an active silicon cochlea

Zhak, Serhii M
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 181 p.
ENG
Relevância na Pesquisa
28.070862%
Silicon cochleas are inspired by the biological cochlea and perform efficient spectrum analysis: They realize a bank of constant-Q Nth-order filters with O(N) efficiency rather than O(N²) efficiency due to their use of an exponentially tapered filter cascade. They are useful in speech-recognition front ends, cochlear implants, and hearing aids, especially as architectures for improving spectral analysis in noisy environments and for performing low-power spectrum analysis. In this thesis I describe four contributions towards improving the state-of-the-art in silicon-cochlea design, two of which involve theoretical modeling, and two of which involve integrated-circuit design. On the theoretical side, I first show that a simple rational approximation to distributed partition impedances in the biological cochlea captures its essential features and enables an efficient artificial implementation achieving maximum gain in a minimum number of stages while still maintaining stability. In particular, I show that the terminating impedance of the cochlea is crucial for its stability and discuss various analytic methods for termination. Second, I derive a novel composite artificial cochlear architecture composed of a cascade of all-pass second-order filters from a first-principles analysis of the biological cochlear transmission line. The novel all-pass architecture reduces phase lag and group delay in the silicon cochlea...