Loss of function of Ywhah in mice induces deafness and cochlear outer hair cells' degeneration.

In vertebrates, 14-3-3 proteins form a family of seven highly conserved isoforms with chaperone activity, which bind phosphorylated substrates mostly involved in regulatory and checkpoint pathways. 14-3-3 proteins are the most abundant protein in the brain and are abundantly found in the cerebrospinal fluid in neurodegenerative diseases, suggesting a critical role in neuron physiology and death. Here we show that 14-3-3eta-deficient mice displayed auditory impairment accompanied by cochlear hair cells' degeneration. We show that 14-3-3eta is highly expressed in the outer and inner hair cells, spiral ganglion neurons of cochlea and retinal ganglion cells. Screening of YWHAH, the gene encoding the 14-3-3eta isoform, in non-syndromic and syndromic deafness, revealed seven non-synonymous variants never reported before. Among them, two were predicted to be damaging in families with syndromic deafness. In vitro, variants of YWHAH induce mild mitochondrial fragmentation and severe susceptibility to apoptosis, in agreement with a reduced capacity of mutated 14-3-3eta to bind the pro-apoptotic Bad protein. This study demonstrates that YWHAH variants can have a substantial effect on 14-3-3eta function and that 14-3-3eta could be a critical factor in the survival of outer hair cells.

Measurement of endolymphatic pressure.

Endolymphatic pressure measurement is of interest both to researchers in the physiology and pathophysiology of hearing and ENT physicians dealing with Menière's disease or similar conditions. It is generally agreed that endolymphatic hydrops is associated with Menière's disease and is accompanied by increased hydrostatic pressure. Endolymphatic pressure, however, cannot be measured precisely without endangering hearing, making the association between hydrops and increased endolymphatic pressure difficult to demonstrate. Several integrated in vivo models have been developed since the 1960s, but only a few allow measurement of endolymphatic hydrostatic pressure. Models associating measurement of hydrostatic pressure and endolymphatic potential and assessment of cochlear function are of value to elucidate the pathophysiology of endolymphatic hydrops. The present article presents the main types of models and discusses their respective interest.

Patient satisfaction and functional results with the bone-anchored hearing aid (BAHA).

OBJECTIVES: To assess patient satisfaction with bone-anchored hearing aids (BAHA) and the role of preoperative audiometric testing. PATIENTS AND METHODS: A telephone satisfaction survey was conducted on all patients implanted between June 1, 2005 and February 1, 2008. Patients with unilateral total deafness underwent preoperative audiometric tests in quiet and in noise and stereoaudiometry with and without BAHA. Patients with a conductive hearing loss underwent preoperative audiometric tests in quiet and in noise and real-life testing at home using a headband. A standardized satisfaction questionnaire derived from the Entific BAHA questionnaire was used. RESULTS: Twenty-two out of 26 patients responded to the questionnaire. Ten patients were implanted for conductive hearing loss (CHL) and 12 for unilateral total deafness (UTD). Mean follow-up was 19 months in the UTD group and 21 months in the CHL group. Sixty-seven percent of UTD and 80% of CHL patients reported improved quality of life. The BAHA was worn for more than 4hours per day by 83% of UTD and 100% of CHL patients, and at least 5 days per week by 67% of UTD and 80% of CHL patients. CONCLUSION: BAHAs provided real benefit in all situations for CHL patients. In UTD, its benefit basically related to noisy environments. In UTD, satisfaction on preoperative stereoaudiometric testing in noise with and without BAHA was predictive of postimplantation satisfaction. In response to the question "Would you do it again?", 81% of patients answered "Yes".

Non-invasive measurements of intralabyrinthine pressure changes by electrocochleography and otoacoustic emissions.

By varying the mechanical load on the stapes footplate, intralabyrinthine pressure (ILP) influences the stiffness of the middle ear and modifies its transfer function. This results in a characteristic phase shift of the otoacoustic emissions (OAEs) around 1kHz [Buki, B., Avan, P., Lemaire, J.J., Dordain, M., Chazal, J., Ribari, O., 1996. Otoacoustic emissions: a new tool for monitoring intracranial pressure changes through stapes displacements. Hear. Res. 94, 125-139]. This finding provides non-invasive means of monitoring changes of ILP and indirectly of intracranial pressure. Yet the vulnerability of OAEs to sensorineural hearing loss excludes many patients from being monitored in this manner. Being dependent on the middle-ear transfer function, the phase of the cochlear microphonic potential (CM) around 1kHz should also respond to ILP changes while being less affected by impaired hearing than OAEs. Here, normal volunteers were subjected to body tilt resulting in stepwise changes in their intracranial pressure and ILP. Their CM around 1kHz was recorded by extratympanic electrocochleography and its dependence on body position was compared to that of distortion-product OAEs. The posture-induced CM changes were also monitored in ears with sensorineural deafness and impaired OAEs to assess the usefulness of CM in the presence of hearing impairment. Last, OAEs and CM were simultaneously monitored in gerbils during intracranial pressure changes brought about via an intracranial catheter. The phase and level shifts induced by body tilt in man and intracranial pressure changes in gerbils showed up both in distortion-product OAEs and CM with similar time courses. In normally-hearing subjects, the mean phase shifts reached 16.3 degrees for CM and 41.6 degrees for OAEs, and CM remained large enough in hearing-impaired subjects for ILP to be monitored. The ratio of about two of OAEs to CM phase shifts matched the prediction of middle-ear models allowing for the fact that CM does not travel back through the middle ear while OAEs do. It follows that CM phase around 1kHz provides non-invasive access to ILP changes even if OAEs cannot be measured due to sensorineural hearing loss.

Vitamin A is a necessary factor for sympathetic-independent rhythmic activation of mitogen-activated protein kinase in the rat pineal gland.

The circadian clock in the suprachiasmatic nucleus (SCN) controls day-to-day physiology and behavior by sending timing messages to multiple peripheral oscillators. In the pineal gland, a major SCN target, circadian events are believed to be driven exclusively by the rhythmic release of norepinephrine from superior cervical ganglia (SCG) neurons relaying clock messages through a polysynaptic pathway. Here we show in rat an SCN-driven daily rhythm of pineal MAPK activation that is not dependent on the SCG and whose maintenance requires vitamin A as a blood-borne factor. This finding challenges the dogma that SCG-released norepinephrine is an exclusive mediator of SCN-pineal communication and allows the assumption that humoral mechanisms are involved in pineal integration of temporal messages.

Sympathectomy improves the ear's resistance to acoustic trauma--could stress render the ear more sensitive?

Emotional stress is a phenomenon experienced by many people at some time in their lives. Some of its early manifestations, such as unbearable loudness of ambient sounds and sensations of dizziness, might be linked to inner ear dysfunction. Although the inner ear is supplied with a substantial sympathetic innervation, previous studies have failed to demonstrate any significant functional impact. We show here that in the awake guinea pig and following unilateral ablation of the superior cervical ganglion, the temporary threshold shift induced by a 1-min exposure to 8 kHz pure tone at 96 dB sound pressure level was reduced by as much as 40 dB. Of interest, the protective effect was bilateral suggesting an intimate relationship between the sympathetic and the olivocochlear efferent systems. The data presented here provide new evidence for a key role for the sympathetic system in modulating temporary threshold shifts following exposure to moderate sound stimulation. This opens new perspectives for investigation of sympathetic control in noise-induced permanent hearing losses.