Wolfram syndrome (WS) is a rare neurodegenerative disease encompassing diabetes mellitus, diabete... more Wolfram syndrome (WS) is a rare neurodegenerative disease encompassing diabetes mellitus, diabetes insipidus, optic atrophy, hearing loss (HL) and neurological disorders. None of the animal models of the pathology are presenting with an early onset HL, impeding the understanding of the role of Wolframin (WFS1), the protein responsible for WS, in the auditory pathway. We generated a knock-in mouse, the Wfs1 E864K line, presenting a human mutation leading to severe deafness in affected individuals. The homozygous mice showed a profound post-natal HL and vestibular syndrome, associated with a decrease of the endocochlear potential (EP) and a devastating alteration of the stria vascularis and neurosensory epithelium. The mutant protein prevented the localization to the cell surface of the Na + /K + ATPase-β1 subunit, a key protein for the maintenance of the EP. Overall, our data support an important role of WFS1 in the maintenance of the EP and the stria vascularis, via its binding partner, the Na + /K + ATPase β1-subunit.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
BackgroundAge-related hearing loss (ARHL), also known as presbycusis, is the most common sensory ... more BackgroundAge-related hearing loss (ARHL), also known as presbycusis, is the most common sensory impairment seen in elderly people. However, the cochlear aging process does not affect people uniformly, suggesting that both genetic and environmental (e.g., noise, ototoxic drugs) factors and their interaction may influence the onset and severity of ARHL. Considering the potential links between thyroid hormone, mitochondrial activity, and hearing, here, we probed the role of p43, a N-terminally truncated and ligand-binding form of the nuclear receptor TRα1, in hearing function and in the maintenance of hearing during aging in p43−/−mice through complementary approaches, including in vivo electrophysiological recording, ultrastructural assessments, biochemistry, and molecular biology.ResultsWe found that the p43−/−mice exhibit no obvious hearing loss in juvenile stages, but that these mice developed a premature, and more severe, ARHL resulting from the loss of cochlear sensory outer and...
Sound-level coding in the auditory nerve is achieved through the progressive recruitment of audit... more Sound-level coding in the auditory nerve is achieved through the progressive recruitment of auditory nerve fibers (ANFs) that differ in threshold of activation and in the stimulus level at which the spike rate saturates. To investigate the functional state of the ANFs, the electrophysiological tests routinely used in clinics only capture the first action potentials firing in synchrony at the onset of the acoustic stimulation. Assessment of other properties (e.g., spontaneous rate and adaptation time constants) requires single-fiber recordings directly from the nerve, which for ethical reasons is not allowed in humans. By combining neuronal activity measurements at the round window and signal-processing algorithms, we constructed a peristimulus time response (PSTR), with a waveform similar to the peristimulus time histograms (PSTHs) derived from single-fiber recordings in young adult female gerbils. Simultaneous recordings of round-window PSTR and single-fiber PSTH provided models to...
Viral-mediated gene augmentation, silencing, or editing offers tremendous promise for the treatme... more Viral-mediated gene augmentation, silencing, or editing offers tremendous promise for the treatment of inherited and acquired deafness. Inner-ear gene therapies often require a safe, clinically useable and effective route of administration to target both ears, while avoiding damage to the delicate structures of the inner ear. Here, we examined the possibility of using a cisterna magna injection as a new cochlear local route for initiating binaural transduction by different serotypes of the adeno-associated virus (AAV2/8, AAV2/9, AAV2/Anc80L65). The results were compared with those following canalostomy injection, one of the existing standard inner ear local delivery routes. Our results demonstrated that a single injection of AAVs enables high-efficiency binaural transduction of almost all inner hair cells with a basal-apical pattern and of large numbers of spiral ganglion neurons of the basal portion of the cochlea, without affecting auditory function and cochlear structures. Taken ...
NMDA receptors (NMDARs) populate the complex between inner hair cell (IHC) and spiral ganglion ne... more NMDA receptors (NMDARs) populate the complex between inner hair cell (IHC) and spiral ganglion neurons (SGNs) in the developing and mature cochlea. However, in the mature cochlea, activation of NMDARs is thought to mainly occur under pathological conditions such as excitotoxicity. Ototoxic drugs such as aspirin enable cochlear arachidonic-acid-sensitive NMDAR responses, and induced chronic tinnitus was blocked by local application of NMDAR antagonists into the cochlear fluids. We largely ignore if other modulators are also engaged. In the brain, D-serine is the primary physiological co-agonist of synaptic NMDARs. Whether D-serine plays a role in the cochlea had remained unexplored. We now reveal the presence of D-serine and its metabolic enzymes prior to, and at hearing onset, in the sensory and non-neuronal cells of the cochlea of several vertebrate species. In vivo intracochlear perfusion of D-serine in guinea pigs reduces sound-evoked activity of auditory nerve fibers without aff...
Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a member of the vasoactive intestina... more Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a member of the vasoactive intestinal polypeptide (VIP)-the secretin-glucagon family of neuropeptides. They act through two classes of receptors: PACAP type 1 (PAC1) and type 2 (VPAC1 and VPAC2). Among their pleiotropic effects throughout the body, PACAP functions as neuromodulators and neuroprotectors, rescuing neurons from apoptosis, mostly through the PAC1 receptor. To explore the potential protective effect of endogenous PACAP against Noise-induced hearing loss (NIHL), we used a knockout mouse model lacking PAC1 receptor expression (PACR1−/−) and a transgenic humanized mouse model expressing the human PAC1 receptor (TgHPAC1R). Based on complementary approaches combining electrophysiological, histochemical, and molecular biological evaluations, we show PAC1R expression in spiral ganglion neurons and in cochlear apical cells of the organ of Corti. Wild-type (WT), PAC1R−/−, and TgHPAC1R mice exhibit similar auditory thres...
The apex or apical region of the cochlear spiral within the inner ear encodes for low‐frequency s... more The apex or apical region of the cochlear spiral within the inner ear encodes for low‐frequency sounds. The disposition of sensory hair cells on the organ of Corti is largely variable in the apical region of mammals, and it does not necessarily follow the typical three‐row pattern of outer hair cells (OHCs). As most underwater noise sources contain low‐frequency components, we expect to find most lesions in the apical region of the cochlea of toothed whales, in cases of permanent noise‐induced hearing loss. To further understand how man‐made noise might affect cetacean hearing, there is a need to describe normal morphological features of the apex and document interspecific anatomic variations in cetaceans. However, distinguishing between apical normal variability and hair cell death is challenging. We describe anatomical features of the organ of Corti of the apex in 23 ears from five species of toothed whales (harbor porpoise Phocoena phocoena, spinner dolphin Stenella longirostris,...
Introduction Current literature does not provide strong evidence that remote programming of heari... more Introduction Current literature does not provide strong evidence that remote programming of hearing aids is effective, despite its increasing use by audiologists. We tested speech perception outcomes, real-ear insertion gain, and changes in self-perceived hearing impairment after face-to-face and remote programming of hearing aids in a randomized multicentre, single-blind crossover study. Methods Adult experienced hearing aid users were enrolled during routine follow-up visits to audiology clinics. Hearing aids were programmed both face to face and remotely, then participants randomly received either the face-to-face or remote settings in a blinded manner and were evaluated 5 weeks later. Participants then received the other settings and were evaluated 5 weeks later. Results Data from 52 out of 60 participants were analysed. We found excellent concordance in performance of hearing aids programmed face to face and remotely for speech understanding in quiet (phonetically balanced kind...
El 16% de la poblacion adulta y un 50% de las personas mayores de 75 anos presentan trastornos au... more El 16% de la poblacion adulta y un 50% de las personas mayores de 75 anos presentan trastornos auditivos (sorderas, acufenos). Debido al aumento de la esperanza de vida y a la exposicion al ruido, que acelera el envejecimiento, muchas personas mejorarian su audicion con una adaptacion audioprotesica. En la actualidad, casi todas las audioprotesis son digitales y con conexion inalambrica. Estos dispositivos pueden ser retroauriculares, que se colocan sobre el pabellon, o intraauriculares, disimulados mas o menos en el conducto auditivo externo. El fundamento de estos aparatos es amplificar la informacion pertinente (en particular el habla) para dirigirla hacia el timpano. En este articulo, se describe el funcionamiento y las estrategias de tratamiento de la senal para adaptarse a las diversas situaciones auditivas de los pacientes. Sin duda, la adaptacion protesica se basa en un proceso cientifico, en particular porque se apoya en un estudio audiologico completo y en programas informaticos de tratamiento de la senal sofisticados. Sin embargo, el exito de la adaptacion audioprotesica requiere tambien una rehabilitacion del paciente, asi como un acompanamiento personalizado y frecuente para lograr un ajuste adaptado a la sordera, al entorno, a la vida y a las expectativas de la persona con sordera.
Il 16% della popolazione adulta e una persona su due oltre i 75 anni soffrono di disturbi uditivi... more Il 16% della popolazione adulta e una persona su due oltre i 75 anni soffrono di disturbi uditivi (sordita, acufeni). Visto l’aumento della speranza di vita e l’esposizione al rumore che accelera l’invecchiamento, molte persone avranno dei benefici nell’uso di apparecchi. Oggi, praticamente tutti gli apparecchi acustici sono digitali e connessi. Questi dispositivi si presentano come retroauricolari indossati sul padiglione o come intrauricolari piu o meno nascosti nel condotto uditivo esterno. Il principio di questi apparecchi e di amplificare l’informazione pertinente (in particolare il discorso) per avviarla vicino al timpano. Questo articolo descrive il funzionamento e le strategie di elaborazione del segnale per adattarsi alle diverse situazioni di ascolto dei pazienti. Certamente, l’adattamento protesico si basa su un approccio scientifico, soprattutto perche si basa su un bilancio audiologico completo e su dei software di trattamento del segnale sofisticati. Tuttavia, il successo di un apparecchio si basa anche su una gestione rieducativa del paziente, cosi come su un supporto personalizzato e regolare per arrivare a una regolazione adeguata alla sordita, all’ambiente, alla vita e alle aspettative dell’ipoudente.
Click here to view linked References Highlights : In female Sprague-Dawley, auditory periphery ... more Click here to view linked References Highlights : In female Sprague-Dawley, auditory periphery aged remarkably well: the auditory nerve threshold and the number of synapses between IHC and fibers were stable. Signs of aging of the central auditory system, albeit modest, were detectable in absence of peripheral alterations At the oldest tested age, behavioral performance was lower. Intrinsic, central aging effects can affect the perception of acoustic stimuli independently of the effects of aging on peripheral receptors
In our aging society, age-related hearing loss (ARHL) has become a major socioeconomic issue. Rea... more In our aging society, age-related hearing loss (ARHL) has become a major socioeconomic issue. Reactive oxygen species (ROS) may be one of the main causal factors of age-related cochlear cell degeneration. We examined whether ROS-induced DNA damage response drives cochlear cell senescence and contributes to ARHL from the cellular up to the system level. Our results revealed that sublethal concentrations of hydrogen peroxide (H 2 O 2) exposure initiated a DNA damage response illustrated by increased γH2AX and 53BP1 expression and foci formation mainly in sensory hair cells, together with increased levels of p-Chk2 and p53. Interestingly, postmitotic cochlear cells exposed to H 2 O 2 displayed key hallmarks of senescent cells, including dramatically increased levels of p21, p38, and p-p38 expression, concomitant with decreased p19 and BubR1 expression and positive senescence-associated β-galactosidase labeling. Importantly, the synthetic superoxide dismutase/catalase mimetic EUK-207 attenuated H 2 O 2-induced DNA damage and senescence phenotypes in cochlear cells in vitro. Furthermore, systemic administration of EUK-207 reduced age-related loss of hearing and hair cell degeneration in senescence-accelerated mouse-prone 8 (SAMP8) mice. Altogether, these findings highlight that ROS-induced DNA damage responses drive cochlear cell senescence and contribute to accelerated ARHL. EUK-207 and likely other antioxidants with similar mechanisms of action could potentially postpone cochlear aging and prevent ARHL in humans.
During development, the sensory cells of the cochlea, the inner hair cells (IHCs), fire spontaneo... more During development, the sensory cells of the cochlea, the inner hair cells (IHCs), fire spontaneous calcium action potentials. This activity at the pre-hearing stage allows the IHCs to autonomously excite the auditory nerve fibers and hence, represents an efficient mechanism to shape the tonotopic organization along the ascending auditory pathway. Using calcium imaging, we show that the activity in the developing cochlea consists of calcium waves that propagate across the supporting and sensory cells. Both basal and apical IHCs were characterized by similar spontaneous calcium transients interspaced with silent periods, consistent with bursts of action potentials recorded in patch-clamp. In addition, adjacent auditory hair cells tend to have a synchronized [Ca 2+ ] i activity, irrespective of their location along the base-to-apex gradient of the cochlea. Finally, we show that the mechanical ablation of the inner phalangeal cells (IPCs), a class of supporting cells, reduces the synchronized [Ca 2+ ] i activity between neighboring sensory cells. These findings support the hypothesis that the tonotopic map refinement in higher auditory centers would depend on the synchronization of a discrete number of auditory sensory cells.
Compound auditory nerve action potentials (CAP) have been extensively used in the evaluation of d... more Compound auditory nerve action potentials (CAP) have been extensively used in the evaluation of drug ototoxicity. Electrophysiological changes observed after aminoglycoside treatment consist of a threshold elevation, an increase in CAP latency near threshold, and a modification of the amplitude of the CAP response as a function of the stimulus intensity (amplitude-intensity function) (see Aran, 1981). The action potential timing curves (APTC) measured with either a forward or a simultaneous masking paradigm also reveal a deterioration in cochlear frequency selectivity in aminoglycoside-treated animals (Harrison and Aran, 1981). However, these alterations have only been observed with high doses of antibiotics and very few reports have been concerned with the early detection of CAP changes following low-dose aminoglycoside treatment. The purpose of the present paper was to investigate in the rat the dose-dependent changes following administration of a range of amikacin doses, with emphasis on the effects of a weak intoxication.
Proceedings of the National Academy of Sciences, 2014
Significance Sensory inner hair cells (IHCs) of the cochlea, the organ of hearing, fire action po... more Significance Sensory inner hair cells (IHCs) of the cochlea, the organ of hearing, fire action potentials during development. This presensory activity likely drives refinement of the ascending auditory pathway. Our study shows that the IHCs fire spontaneous bursts of action potentials, which tend to occur at a regular time interval and have a similar length toward the end of the first postnatal week. The spiking behavior does not depend on ATP but, rather, is modulated by the α9α10 nicotinic receptor, which is expressed by the developing IHCs. The firing pattern of the IHCs may therefore convey a temporal signature of the cochlear development to the higher auditory centers.
Before acquiring their mature state, cochlear hair cells undergo a series of changes in expressio... more Before acquiring their mature state, cochlear hair cells undergo a series of changes in expression of ion channels. How this complex mechanism is achieved is not fully understood. Tmprss3, a type II serine protease expressed in hair cells, is required for their proper functioning at the onset of hearing. To unravel the role of Tmprss3 in the acquisition of mature K 1 currents, we compared their function by patch-clamp technique in wild-type Tmprss3 WT and Tmprss3 Y260X-mutant mice. Interestingly, only outward K 1 currents were altered in Tmprss3 Y260X-mutant mice. To determine by which mechanism this occurred, we compared the protein network of Tmprss3 WT and Tmprss3 Y260X-mutant mice using proteomic analysis. This led to the identification of a pathway related to potassium Kcnma1 channels. This pathway was validated by immunohistochemistry, focusing on the most downregulated protein that was identified as a cochlear Kcnma1-associated protein, APOA1. Finally, we show that, in contrast to Tmprss3 WT , Kcnma1 channels were absent at the neck of inner hair cells (IHCs) in Tmprss3 Y260X-mutant mice. In conclusion, our data suggest that lack of Tmprss3 leads to a decrease in Kcnma1 potassium channels expression in (IHCs).
To investigate a possible involvement of protein kinase C (PKC) in cochlear efferent neurotransmi... more To investigate a possible involvement of protein kinase C (PKC) in cochlear efferent neurotransmission, we studied the expression of the calcium‐dependent PKC beta II isoform in the rat organ of Corti at different postnatal ages using immunofluorescence and immunoelectron microscopy. We found evidence of PKC beta II as early as postnatal day (PND) 5 in efferent axons running in the inner spiral bundle and in Hensen cells. At PND 8, we also found PKC beta II in efferents targeting outer hair cells (OHCs), and a slight detection at the synaptic pole in the first row of the basal and middle cochlear turns. At PND 12, PKC beta II expression declined in the efferent fibres contacting OHCs, whereas expression was concentrated at the postsynaptic membrane, from the basal and middle turns. The adult‐like pattern of PKC beta II distribution was observed at PND 20. Throughout the cochlea, we found PKC beta II expression in the Hensen cells, non‐sensory cells involved in potassium re‐cycling, ...
The masking phenomenon is used in clinical investigation of the inner ear to determine the freque... more The masking phenomenon is used in clinical investigation of the inner ear to determine the frequency selectivity properties of the auditory system. Sectioning of the crossed part of the medial efferent bundle in a guinea pig model decreases the simultaneous masking phenomenon. The efferent effect seen in the forward masking varied with the masking paradigm used. When the masker onset
Wolfram syndrome (WS) is a rare neurodegenerative disease encompassing diabetes mellitus, diabete... more Wolfram syndrome (WS) is a rare neurodegenerative disease encompassing diabetes mellitus, diabetes insipidus, optic atrophy, hearing loss (HL) and neurological disorders. None of the animal models of the pathology are presenting with an early onset HL, impeding the understanding of the role of Wolframin (WFS1), the protein responsible for WS, in the auditory pathway. We generated a knock-in mouse, the Wfs1 E864K line, presenting a human mutation leading to severe deafness in affected individuals. The homozygous mice showed a profound post-natal HL and vestibular syndrome, associated with a decrease of the endocochlear potential (EP) and a devastating alteration of the stria vascularis and neurosensory epithelium. The mutant protein prevented the localization to the cell surface of the Na + /K + ATPase-β1 subunit, a key protein for the maintenance of the EP. Overall, our data support an important role of WFS1 in the maintenance of the EP and the stria vascularis, via its binding partner, the Na + /K + ATPase β1-subunit.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
BackgroundAge-related hearing loss (ARHL), also known as presbycusis, is the most common sensory ... more BackgroundAge-related hearing loss (ARHL), also known as presbycusis, is the most common sensory impairment seen in elderly people. However, the cochlear aging process does not affect people uniformly, suggesting that both genetic and environmental (e.g., noise, ototoxic drugs) factors and their interaction may influence the onset and severity of ARHL. Considering the potential links between thyroid hormone, mitochondrial activity, and hearing, here, we probed the role of p43, a N-terminally truncated and ligand-binding form of the nuclear receptor TRα1, in hearing function and in the maintenance of hearing during aging in p43−/−mice through complementary approaches, including in vivo electrophysiological recording, ultrastructural assessments, biochemistry, and molecular biology.ResultsWe found that the p43−/−mice exhibit no obvious hearing loss in juvenile stages, but that these mice developed a premature, and more severe, ARHL resulting from the loss of cochlear sensory outer and...
Sound-level coding in the auditory nerve is achieved through the progressive recruitment of audit... more Sound-level coding in the auditory nerve is achieved through the progressive recruitment of auditory nerve fibers (ANFs) that differ in threshold of activation and in the stimulus level at which the spike rate saturates. To investigate the functional state of the ANFs, the electrophysiological tests routinely used in clinics only capture the first action potentials firing in synchrony at the onset of the acoustic stimulation. Assessment of other properties (e.g., spontaneous rate and adaptation time constants) requires single-fiber recordings directly from the nerve, which for ethical reasons is not allowed in humans. By combining neuronal activity measurements at the round window and signal-processing algorithms, we constructed a peristimulus time response (PSTR), with a waveform similar to the peristimulus time histograms (PSTHs) derived from single-fiber recordings in young adult female gerbils. Simultaneous recordings of round-window PSTR and single-fiber PSTH provided models to...
Viral-mediated gene augmentation, silencing, or editing offers tremendous promise for the treatme... more Viral-mediated gene augmentation, silencing, or editing offers tremendous promise for the treatment of inherited and acquired deafness. Inner-ear gene therapies often require a safe, clinically useable and effective route of administration to target both ears, while avoiding damage to the delicate structures of the inner ear. Here, we examined the possibility of using a cisterna magna injection as a new cochlear local route for initiating binaural transduction by different serotypes of the adeno-associated virus (AAV2/8, AAV2/9, AAV2/Anc80L65). The results were compared with those following canalostomy injection, one of the existing standard inner ear local delivery routes. Our results demonstrated that a single injection of AAVs enables high-efficiency binaural transduction of almost all inner hair cells with a basal-apical pattern and of large numbers of spiral ganglion neurons of the basal portion of the cochlea, without affecting auditory function and cochlear structures. Taken ...
NMDA receptors (NMDARs) populate the complex between inner hair cell (IHC) and spiral ganglion ne... more NMDA receptors (NMDARs) populate the complex between inner hair cell (IHC) and spiral ganglion neurons (SGNs) in the developing and mature cochlea. However, in the mature cochlea, activation of NMDARs is thought to mainly occur under pathological conditions such as excitotoxicity. Ototoxic drugs such as aspirin enable cochlear arachidonic-acid-sensitive NMDAR responses, and induced chronic tinnitus was blocked by local application of NMDAR antagonists into the cochlear fluids. We largely ignore if other modulators are also engaged. In the brain, D-serine is the primary physiological co-agonist of synaptic NMDARs. Whether D-serine plays a role in the cochlea had remained unexplored. We now reveal the presence of D-serine and its metabolic enzymes prior to, and at hearing onset, in the sensory and non-neuronal cells of the cochlea of several vertebrate species. In vivo intracochlear perfusion of D-serine in guinea pigs reduces sound-evoked activity of auditory nerve fibers without aff...
Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a member of the vasoactive intestina... more Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a member of the vasoactive intestinal polypeptide (VIP)-the secretin-glucagon family of neuropeptides. They act through two classes of receptors: PACAP type 1 (PAC1) and type 2 (VPAC1 and VPAC2). Among their pleiotropic effects throughout the body, PACAP functions as neuromodulators and neuroprotectors, rescuing neurons from apoptosis, mostly through the PAC1 receptor. To explore the potential protective effect of endogenous PACAP against Noise-induced hearing loss (NIHL), we used a knockout mouse model lacking PAC1 receptor expression (PACR1−/−) and a transgenic humanized mouse model expressing the human PAC1 receptor (TgHPAC1R). Based on complementary approaches combining electrophysiological, histochemical, and molecular biological evaluations, we show PAC1R expression in spiral ganglion neurons and in cochlear apical cells of the organ of Corti. Wild-type (WT), PAC1R−/−, and TgHPAC1R mice exhibit similar auditory thres...
The apex or apical region of the cochlear spiral within the inner ear encodes for low‐frequency s... more The apex or apical region of the cochlear spiral within the inner ear encodes for low‐frequency sounds. The disposition of sensory hair cells on the organ of Corti is largely variable in the apical region of mammals, and it does not necessarily follow the typical three‐row pattern of outer hair cells (OHCs). As most underwater noise sources contain low‐frequency components, we expect to find most lesions in the apical region of the cochlea of toothed whales, in cases of permanent noise‐induced hearing loss. To further understand how man‐made noise might affect cetacean hearing, there is a need to describe normal morphological features of the apex and document interspecific anatomic variations in cetaceans. However, distinguishing between apical normal variability and hair cell death is challenging. We describe anatomical features of the organ of Corti of the apex in 23 ears from five species of toothed whales (harbor porpoise Phocoena phocoena, spinner dolphin Stenella longirostris,...
Introduction Current literature does not provide strong evidence that remote programming of heari... more Introduction Current literature does not provide strong evidence that remote programming of hearing aids is effective, despite its increasing use by audiologists. We tested speech perception outcomes, real-ear insertion gain, and changes in self-perceived hearing impairment after face-to-face and remote programming of hearing aids in a randomized multicentre, single-blind crossover study. Methods Adult experienced hearing aid users were enrolled during routine follow-up visits to audiology clinics. Hearing aids were programmed both face to face and remotely, then participants randomly received either the face-to-face or remote settings in a blinded manner and were evaluated 5 weeks later. Participants then received the other settings and were evaluated 5 weeks later. Results Data from 52 out of 60 participants were analysed. We found excellent concordance in performance of hearing aids programmed face to face and remotely for speech understanding in quiet (phonetically balanced kind...
El 16% de la poblacion adulta y un 50% de las personas mayores de 75 anos presentan trastornos au... more El 16% de la poblacion adulta y un 50% de las personas mayores de 75 anos presentan trastornos auditivos (sorderas, acufenos). Debido al aumento de la esperanza de vida y a la exposicion al ruido, que acelera el envejecimiento, muchas personas mejorarian su audicion con una adaptacion audioprotesica. En la actualidad, casi todas las audioprotesis son digitales y con conexion inalambrica. Estos dispositivos pueden ser retroauriculares, que se colocan sobre el pabellon, o intraauriculares, disimulados mas o menos en el conducto auditivo externo. El fundamento de estos aparatos es amplificar la informacion pertinente (en particular el habla) para dirigirla hacia el timpano. En este articulo, se describe el funcionamiento y las estrategias de tratamiento de la senal para adaptarse a las diversas situaciones auditivas de los pacientes. Sin duda, la adaptacion protesica se basa en un proceso cientifico, en particular porque se apoya en un estudio audiologico completo y en programas informaticos de tratamiento de la senal sofisticados. Sin embargo, el exito de la adaptacion audioprotesica requiere tambien una rehabilitacion del paciente, asi como un acompanamiento personalizado y frecuente para lograr un ajuste adaptado a la sordera, al entorno, a la vida y a las expectativas de la persona con sordera.
Il 16% della popolazione adulta e una persona su due oltre i 75 anni soffrono di disturbi uditivi... more Il 16% della popolazione adulta e una persona su due oltre i 75 anni soffrono di disturbi uditivi (sordita, acufeni). Visto l’aumento della speranza di vita e l’esposizione al rumore che accelera l’invecchiamento, molte persone avranno dei benefici nell’uso di apparecchi. Oggi, praticamente tutti gli apparecchi acustici sono digitali e connessi. Questi dispositivi si presentano come retroauricolari indossati sul padiglione o come intrauricolari piu o meno nascosti nel condotto uditivo esterno. Il principio di questi apparecchi e di amplificare l’informazione pertinente (in particolare il discorso) per avviarla vicino al timpano. Questo articolo descrive il funzionamento e le strategie di elaborazione del segnale per adattarsi alle diverse situazioni di ascolto dei pazienti. Certamente, l’adattamento protesico si basa su un approccio scientifico, soprattutto perche si basa su un bilancio audiologico completo e su dei software di trattamento del segnale sofisticati. Tuttavia, il successo di un apparecchio si basa anche su una gestione rieducativa del paziente, cosi come su un supporto personalizzato e regolare per arrivare a una regolazione adeguata alla sordita, all’ambiente, alla vita e alle aspettative dell’ipoudente.
Click here to view linked References Highlights : In female Sprague-Dawley, auditory periphery ... more Click here to view linked References Highlights : In female Sprague-Dawley, auditory periphery aged remarkably well: the auditory nerve threshold and the number of synapses between IHC and fibers were stable. Signs of aging of the central auditory system, albeit modest, were detectable in absence of peripheral alterations At the oldest tested age, behavioral performance was lower. Intrinsic, central aging effects can affect the perception of acoustic stimuli independently of the effects of aging on peripheral receptors
In our aging society, age-related hearing loss (ARHL) has become a major socioeconomic issue. Rea... more In our aging society, age-related hearing loss (ARHL) has become a major socioeconomic issue. Reactive oxygen species (ROS) may be one of the main causal factors of age-related cochlear cell degeneration. We examined whether ROS-induced DNA damage response drives cochlear cell senescence and contributes to ARHL from the cellular up to the system level. Our results revealed that sublethal concentrations of hydrogen peroxide (H 2 O 2) exposure initiated a DNA damage response illustrated by increased γH2AX and 53BP1 expression and foci formation mainly in sensory hair cells, together with increased levels of p-Chk2 and p53. Interestingly, postmitotic cochlear cells exposed to H 2 O 2 displayed key hallmarks of senescent cells, including dramatically increased levels of p21, p38, and p-p38 expression, concomitant with decreased p19 and BubR1 expression and positive senescence-associated β-galactosidase labeling. Importantly, the synthetic superoxide dismutase/catalase mimetic EUK-207 attenuated H 2 O 2-induced DNA damage and senescence phenotypes in cochlear cells in vitro. Furthermore, systemic administration of EUK-207 reduced age-related loss of hearing and hair cell degeneration in senescence-accelerated mouse-prone 8 (SAMP8) mice. Altogether, these findings highlight that ROS-induced DNA damage responses drive cochlear cell senescence and contribute to accelerated ARHL. EUK-207 and likely other antioxidants with similar mechanisms of action could potentially postpone cochlear aging and prevent ARHL in humans.
During development, the sensory cells of the cochlea, the inner hair cells (IHCs), fire spontaneo... more During development, the sensory cells of the cochlea, the inner hair cells (IHCs), fire spontaneous calcium action potentials. This activity at the pre-hearing stage allows the IHCs to autonomously excite the auditory nerve fibers and hence, represents an efficient mechanism to shape the tonotopic organization along the ascending auditory pathway. Using calcium imaging, we show that the activity in the developing cochlea consists of calcium waves that propagate across the supporting and sensory cells. Both basal and apical IHCs were characterized by similar spontaneous calcium transients interspaced with silent periods, consistent with bursts of action potentials recorded in patch-clamp. In addition, adjacent auditory hair cells tend to have a synchronized [Ca 2+ ] i activity, irrespective of their location along the base-to-apex gradient of the cochlea. Finally, we show that the mechanical ablation of the inner phalangeal cells (IPCs), a class of supporting cells, reduces the synchronized [Ca 2+ ] i activity between neighboring sensory cells. These findings support the hypothesis that the tonotopic map refinement in higher auditory centers would depend on the synchronization of a discrete number of auditory sensory cells.
Compound auditory nerve action potentials (CAP) have been extensively used in the evaluation of d... more Compound auditory nerve action potentials (CAP) have been extensively used in the evaluation of drug ototoxicity. Electrophysiological changes observed after aminoglycoside treatment consist of a threshold elevation, an increase in CAP latency near threshold, and a modification of the amplitude of the CAP response as a function of the stimulus intensity (amplitude-intensity function) (see Aran, 1981). The action potential timing curves (APTC) measured with either a forward or a simultaneous masking paradigm also reveal a deterioration in cochlear frequency selectivity in aminoglycoside-treated animals (Harrison and Aran, 1981). However, these alterations have only been observed with high doses of antibiotics and very few reports have been concerned with the early detection of CAP changes following low-dose aminoglycoside treatment. The purpose of the present paper was to investigate in the rat the dose-dependent changes following administration of a range of amikacin doses, with emphasis on the effects of a weak intoxication.
Proceedings of the National Academy of Sciences, 2014
Significance Sensory inner hair cells (IHCs) of the cochlea, the organ of hearing, fire action po... more Significance Sensory inner hair cells (IHCs) of the cochlea, the organ of hearing, fire action potentials during development. This presensory activity likely drives refinement of the ascending auditory pathway. Our study shows that the IHCs fire spontaneous bursts of action potentials, which tend to occur at a regular time interval and have a similar length toward the end of the first postnatal week. The spiking behavior does not depend on ATP but, rather, is modulated by the α9α10 nicotinic receptor, which is expressed by the developing IHCs. The firing pattern of the IHCs may therefore convey a temporal signature of the cochlear development to the higher auditory centers.
Before acquiring their mature state, cochlear hair cells undergo a series of changes in expressio... more Before acquiring their mature state, cochlear hair cells undergo a series of changes in expression of ion channels. How this complex mechanism is achieved is not fully understood. Tmprss3, a type II serine protease expressed in hair cells, is required for their proper functioning at the onset of hearing. To unravel the role of Tmprss3 in the acquisition of mature K 1 currents, we compared their function by patch-clamp technique in wild-type Tmprss3 WT and Tmprss3 Y260X-mutant mice. Interestingly, only outward K 1 currents were altered in Tmprss3 Y260X-mutant mice. To determine by which mechanism this occurred, we compared the protein network of Tmprss3 WT and Tmprss3 Y260X-mutant mice using proteomic analysis. This led to the identification of a pathway related to potassium Kcnma1 channels. This pathway was validated by immunohistochemistry, focusing on the most downregulated protein that was identified as a cochlear Kcnma1-associated protein, APOA1. Finally, we show that, in contrast to Tmprss3 WT , Kcnma1 channels were absent at the neck of inner hair cells (IHCs) in Tmprss3 Y260X-mutant mice. In conclusion, our data suggest that lack of Tmprss3 leads to a decrease in Kcnma1 potassium channels expression in (IHCs).
To investigate a possible involvement of protein kinase C (PKC) in cochlear efferent neurotransmi... more To investigate a possible involvement of protein kinase C (PKC) in cochlear efferent neurotransmission, we studied the expression of the calcium‐dependent PKC beta II isoform in the rat organ of Corti at different postnatal ages using immunofluorescence and immunoelectron microscopy. We found evidence of PKC beta II as early as postnatal day (PND) 5 in efferent axons running in the inner spiral bundle and in Hensen cells. At PND 8, we also found PKC beta II in efferents targeting outer hair cells (OHCs), and a slight detection at the synaptic pole in the first row of the basal and middle cochlear turns. At PND 12, PKC beta II expression declined in the efferent fibres contacting OHCs, whereas expression was concentrated at the postsynaptic membrane, from the basal and middle turns. The adult‐like pattern of PKC beta II distribution was observed at PND 20. Throughout the cochlea, we found PKC beta II expression in the Hensen cells, non‐sensory cells involved in potassium re‐cycling, ...
The masking phenomenon is used in clinical investigation of the inner ear to determine the freque... more The masking phenomenon is used in clinical investigation of the inner ear to determine the frequency selectivity properties of the auditory system. Sectioning of the crossed part of the medial efferent bundle in a guinea pig model decreases the simultaneous masking phenomenon. The efferent effect seen in the forward masking varied with the masking paradigm used. When the masker onset
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Papers by jean-luc puel