Outer- and middle-ear contributions to presbycusis in the Brown Norway rat

This paper examines the contribution of the outer and middle ears to the hearing loss associated with presbycusis in Brown Norway rats. Animals were formed into two groups; young adults (2-3 months old) and aged animals (approximately 34 months old). Auditory brainstem response (ABR) thresholds were obtained with the outer ear intact or surgically removed. Tympanic membrane (TM) velocity transfer functions were measured from the umbo with the outer ear removed. The length of the auditory meatus, TM surface area, and TM thickness were quantified. The ABR thresholds were 17-26 dB less sensitive in the aged animals between 8.0 and 40.0 kHz when the outer ear was intact. A significant and reliable reduction in the aged rat velocity transfer function of 5-8 dB occurred between 10.0 and 32.0 kHz, while the low frequency velocity response was only a few decibels greater in the younger animals. The ABR threshold differences between young adult and aged ears were compensated by removing the outer/middle ear effects of aging to reveal a purely sensorineural component of presbycusis. The outer and middle ear effects were calculated directly when the ABR and TM velocity data were obtained with the outer ear removed. The outer ear intact condition was modeled in order to compare the ABR data obtained with the outer ear intact with the TM velocity data obtained with the outer removed. With either procedure, removal of the age-related contributions of the outer and middle ear to the ABR threshold resulted in similar age-related ABR threshold shifts between the two age groups. The pure sensorineural threshold shift component of the ABR response was restricted to frequencies between 5.0 and 20.0 kHz and reached a maximum of approximately 15 dB. These results support the conclusion that there is an outer- and middle-ear contribution to the threshold loss defining presbycusis.     

A Chromosome 17 Locus Engenders Frequency-Specific Non-Progressive Hearing Loss that Contributes to Age-Related Hearing Loss in Mice

The 129S6/SvEvTac (129S6) inbred mouse is known for its resistance to noise-induced hearing loss (NIHL). However, less is understood of its unique age-related hearing loss (AHL) phenotype and its potential relationship with the resistance to NIHL. Here, we studied the physiological characteristics of hearing loss in 129S6 and asked if noise resistance (NR) and AHL are genetically linked to the same chromosomal region. We used auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to examine hearing sensitivity between 1 and 13 months of age of recombinant-inbred (congenic) mice with an NR phenotype. We identified a region of proximal chromosome (Chr) 17 (D17Mit143-D17Mit100) that contributes to a sensory, non-progressive hearing loss (NPHL) affecting exclusively the high-frequencies (>24 kHz) and maps to the nr1 locus on Chr 17. ABR experiments showed that 129S6 and CBA/CaJ F1 (CBACa) hybrid mice exhibit normal hearing, indicating that the hearing loss in 129S6 mice is inherited recessively. An allelic complementation test between the 129S6 and 101/H (101H) strains did not rescue hearing loss, suggesting genetic allelism between the nphl and phl1 loci of these strains, respectively. The hybrids had a milder hearing loss than either parental strain, which indicate a possible interaction with other genes in the mouse background or a digenic interaction between different genes that reside in the same genomic region. Our study defines a locus for nphl on Chr 17 affecting frequencies greater than 24 kHz.     

Low-Frequency Tone Pips Elicit Exaggerated Startle Reflexes in C57BL/6J Mice with Hearing Loss

The strength of the acoustic startle reflex (ASR) as a function of age was studied in adult C57BL/6J and CBA/CaJ mice, because altered ASR levels are a potential behavioral consequence of the neural reorganization that accompanies the early-onset hearing loss of the C57BL, in contrast to the normal-hearing CBA. For C57BL mice at 14–36 weeks of age, compared with 7-week-old mice, high-frequency thresholds measured with the auditory brainstem response (ABR) were less sensitive by about 25–30 dB while the hearing loss at low frequencies was 10–15 dB, but by 60 weeks losses of 45–50 dB were present across the entire spectrum. Their ASR amplitudes for 16 kHz tone pips were highest at 7 weeks and then declined with age, but, for 4 kHz tones the ASR increased in strength at 18 weeks and beyond to levels above that of the younger mice. This hyperreactivity persisted even in 60-week-old mice. The ASR for 16 kHz stimuli was positively correlated with hearing sensitivity, but the ASR for 4 kHz stimuli was positively correlated with hearing loss for mice that were 18–36 weeks of age. Furthermore, ASR amplitudes for 4 kHz stimuli were positively correlated with the 16 kHz ASR in young C57BL mice but negatively correlated in older mice. There were no similar ASR or ABR changes in adult CBA mice through 19 weeks of age. Correlations between ASR and ABR scores were always weakly positive, and correlations between 4 kHz and 16 kHz ASR amplitudes were always strongly positive. The ASR data in older C57BL mice with hearing loss are consistent with reports describing their increased neural representation of low-frequency sounds and reinforce the value of this strain for studying the functional consequences that accompany age-related cochlear degeneration.     

Conductive Hearing Loss Induced by Experimental Middle-Ear Effusion in a Chinchilla Model Reveals Impaired Tympanic Membrane-Coupled Ossicular Chain Movement

Otitis media with effusion (OME) occurs when fluid collects in the middle-ear space behind the tympanic membrane (TM). As a result of this effusion, sounds can become attenuated by as much as 30–40 dB, causing a conductive hearing loss (CHL). However, the exact mechanical cause of the hearing loss remains unclear. Possible causes can include altered compliance of the TM, inefficient movement of the ossicular chain, decreased compliance of the oval window-stapes footplate complex, or altered input to the oval and round window due to conduction of sound energy through middle-ear fluid. Here, we studied the contribution of TM motion and umbo velocity to a CHL caused by middle-ear effusion. Using the chinchilla as an animal model, umbo velocity (V _U) and cochlear microphonic (CM) responses were measured simultaneously using sinusoidal tone pip stimuli (125 Hz–12 kHz) before and after filling the middle ear with different volumes (0.5–2.0 mL) of silicone oil (viscosity, 3.5 Poise). Concurrent increases in CM thresholds and decreases in umbo velocity were noted after the middle ear was filled with 1.0 mL or more of fluid. Across animals, completely filling the middle ear with fluid caused 20–40-dB increases in CM thresholds and 15–35-dB attenuations in umbo velocity. Clinic-standard 226-Hz tympanometry was insensitive to fluid-associated changes in CM thresholds until virtually the entire middle-ear cavity had been filled (approximately >1.5 mL). The changes in umbo velocity, CM thresholds, and tympanometry due to experimentally induced OME suggest CHL arises primarily as a result of impaired TM mobility and TM-coupled umbo motion plus additional mechanisms within the middle ear.     

A normative study of tympanic membrane motion in humans using a laser Doppler vibrometer (LDV)

Laser Doppler vibrometry was used to measure the sound-induced tympanic membrane (TM) velocity, assessed near the umbo, in 56 normal hearing human subjects at nine sound frequencies. A second series of measurements was made in 47 subjects with sensorineural hearing loss (SNHL). Each set of measurements has features in common with previously published results. The measured velocity magnitude (normalized by the stimulus sound pressure) at any one frequency ranged among subjects by factors of 3-0.3 (+/-10 dB) from the mean and the phase angle of the normalized velocity ranged from +/-15 degrees around the mean at low frequencies to more than +/-200 degrees around the mean at 6 kHz. Measurements repeated after intervals of minutes to months were generally within 40% in magnitude (+/-3 dB) and 20 degrees in phase. Sources of variability included the effect of small differences in the location of the measurement on the TM and small static middle-ear pressures. No effects of stimulus level, ear sidedness (right or left), gender, age or the presence or absence of SNHL were found. These results provide a baseline normal response for studies of TM velocity with conductive hearing losses of different etiologies.     

Acoustic injury in mice: 129/SvEv is exceptionally resistant to noise-induced hearing loss

20 kHz could not be evaluated. Permanent threshold shift (PTS) and hair cell losses, measured 1 week after high-intensity exposure to an 8-16 kHz noise band, were smaller in129/SvEv at all exposure levels and durations from 97 dB SPLx2 h to 106 dB SPLx8 h. Furthermore, PTS growth with increasing exposure energy was slower in 129/SvEv (<2 dB/dB) than CBA/CaJ (9 dB/dB). These data suggest that the vulnerability differences lie in the inner ear, not the middle ear. Several 129/Sv substrains show age-related hearing loss (AHL): 129/SvEv has not yet been evaluated (Zheng, Q.Y., Johnson, K. R., Erway, L.C., 1999. Assessment of hearing in 80 inbred strains of mice by ABR threshold analyses. Hear. Res. 130, 94-107). Thus, although other strains with AHL, e.g. C57Bl/6J, show increased vulnerability to noise-induced hearing loss (NIHL), pairing of AHL and NIHL vulnerabilities may not be obligatory.     

Forward and reverse transfer functions of the middle ear based on pressure and velocity DPOAEs with implications for differential hearing diagnosis

Recently it was shown that distortion product otoacoustic emissions (DPOAEs) can be measured as vibration of the human tympanic membrane in vivo, and proposed to use these vibration DPOAEs to support a differential diagnosis of middle-ear and cochlear pathologies. Here, we investigate how the reverse transfer function (r-TF), defined as the ratio of DPOAE-velocity of the umbo to DPOAE-pressure in the ear canal, can be used to diagnose the state of the middle ear. Anaesthetized guinea pigs served as the experimental animal. Sound was delivered free-field and the vibration of the umbo measured with a laser Doppler vibrometer (LDV). Sound pressure was measured 2-3 mm from the tympanic membrane with a probe-tube microphone. The forward transfer function (f-TF) of umbo velocity relative to ear-canal pressure was obtained by stimulating with multi-tone pressure. The r-TF was assembled from DPOAE components generated in response to acoustic stimulation with two stimulus tones of frequencies f(1) and f(2); f(2)/f(1) was constant at 1.2. The r-TF was plotted as function of DPOAE frequencies; they ranged from 1.7 kHz to 23 kHz. The r-TF showed a characteristic shape with an anti-resonance around 8 kHz as its most salient feature. The data were interpreted with the aid of a middle-ear transmission-line model taken from the literature for the cat and adapted to the guinea pig. Parameters were estimated with a three-step fitting algorithm. Importantly, the r-TF is governed by only half of the 15 independent, free parameters of the model. The parameters estimated from the r-TF were used to estimate the other half of the parameters from the f-TF. The use of r-TF data - in addition to f-TF data - allowed robust estimates of the middle-ear parameters to be obtained. The results highlight the potential of using vibration DPOAEs for ascertaining the functionality of the middle ear and, therefore, for supporting a differential diagnosis of middle-ear and cochlear pathologies.     

Age-Related Hearing Loss in C57BL/6J Mice has both Frequency-Specific and Non-Frequency-Specific Components that Produce a Hyperacusis-Like Exaggeration of the Acoustic Startle Reflex

Auditory brainstem-evoked response (ABR) thresholds were obtained in a longitudinal study of C57BL/6J mice between 10 and 53 weeks old, with repeated testing every 2 weeks. On alternate weeks, acoustic startle reflex (ASR) amplitudes were measured, elicited by tone pips with stimulus frequencies of 3, 6, 12, and 24 kHz, and intensities from subthreshold up to 110 dB sound pressure level. The increase in ABR thresholds for 3 and 6 kHz test stimuli followed a linear time course with increasing age from 10 to 53 weeks, with a slope of about 0.7 dB/week, and for 48 kHz a second linear time course, but beginning at 10 weeks with a slope of about 2.3 dB/week. ABR thresholds for 12, 24, and 32 kHz increased after one linear segment with a 0.7 dB slope, then after a variable delay related to the test frequency, shifted to a second segment having slopes of 3–5 dB/week. Hearing loss initially reduced the ASR for all eliciting stimuli, but at about 6 months of age, the response elicited by intense 3 and 6 kHz stimuli began to increase to reach values about three times above normal, and previously subthreshold stimuli came to elicit vigorous responses seen at first only for the intense stimuli. This hyperacusis-like effect appeared in all mice but was especially pronounced in mice with more serious hearing loss. These ABR data, together with a review of histopathological data in the C57BL/6 literature, suggest that the non-frequency-specific slow time course of hearing loss results from pathology in the lateral wall of the cochlea, whereas the stimulus-specific hearing loss with a rapid time course results from hair cell loss. Delayed exaggeration of the ASR with hearing loss reveals a deficit in centrifugal inhibitory control over the afferent reflex pathways after central neural reorganization, suggesting that this mouse may provide a useful model of age-related tinnitus and associated hyperacusis.     

Hyperlipidemia and noise in the chinchilla

Chinchillas were maintained on a 1% cholesterol diet for 6 months. Auditory Brainstem Response (ABR) measurements were obtained before and at 1, 3, 5, and 6 months after initiation of diet. Compound Action Potential (AP) measurements were obtained at sacrifice at 6 months. A significant reduction in ABR was seen at 5 months-on-diet. At 5 months, the animals were exposed to a 2 octave bandpass noise centered at 1 kHz at 105 dB for 220 min. One month following noise exposure, the cholesterol-fed animals exhibited a greater ABR latency shift at low intensities, and an elevated AP threshold at higher frequencies, vis-à-vis a control group.     

Mutation of the POU-domain gene Brn4/Pou3f4 affects middle-ear sound conduction in the mouse

Mutagenesis of the POU-domain gene Brn4/Pou3f4 causes defects in the cochlear duct, semicircular canal, temporal bone and stapes footplate. The footplate defect suggested a middle-ear conductive component to the hearing loss associated with this mutation. This was examined by measuring velocity transfer functions at the umbo of wild type and knockout mice during sound stimulation of the tympanic membrane. When the median umbo velocity of test frequencies in the two groups were compared, the mid-range frequencies of the knockout mice showed a statistically reliable reduction in velocity (maximum of 13 dB) and high variability among animals. These results indicated that mutation of the POU-domain gene, Brn4, changed middle-ear sound conduction when measured at the umbo. The origin of the abnormal velocity response was sought by puncturing a hole in the pars flaccida (PF), and subsequently, measuring movements at the umbo and the head of the long arm of the incus. This hole permitted us to measure velocity at the tip of the incus long arm, just above the incudostapedial joint. The comparison of umbo behavior in both groups with PF perforated showed a loss of sensitivity in the mid-range frequencies of the knockout animals. A comparison of incus velocity in the two groups also exhibited a velocity reduction in the mid-range frequencies of the knockout animals. The reduction at the incus, however, was milder than observed at the umbo. The effect of the perforation in, and variability of, the knockout incus responses may have masked a more potent mid-range frequency effect. Nevertheless, evaluation of the stapes and oval window in knockout mice showed variable pathology from ear to ear. The presence of this pathology, the mid-frequency loss in incus sensitivity and the variability in incus velocity among animals suggested that abnormal stapes behavior in Brn4 deficient mice may determine the response of the ossicles, and thus account for the abnormal mid-frequency umbo behavior seen in knockout animals.     

Schall- und Geschwindigkeits-DPOAE

Recent publications show that DPOAE measurements can generate a more accurate diagnosis, if (1) their fine structure is suppressed, and (2) if the calibration of the sound field is improved. Reduction of the fine structure is particularly important in the frequency range below 4 kHz in subjects with intact cochlear amplifier and can reduce the standard deviation of threshold estimations based on DPOAE-input/output functions from 11 dB to 6 dB. Improving the sound-field calibration has most impact in the frequency range above 4 kHz. Threshold estimations based on laserinterferometrically measured DPOAE input-output functions where the sound field was calibrated close to the tympanic membrane have been shown to reduce the standard deviation down to 8.6 dB in humans and 6.5 dB in guinea pigs. Compared with conventional DPOAE measures, such as amplitude or signal-to-noise ratio, threshold estimation based on DPOAE-I/O functions has the advantage that its slope provides additional information about the middle-ear; however, its specificity is limited. In the future, combined methods such as acoustic reflectance or laser vibrometry on the umbo promise a reliable assessment of the middle-ear contribution to DPOAE.     

Age-related loss of distortion product otoacoustic emissions in four mouse strains

Changes in cochlear function in four inbred strains of mice, CBA/CaJ (CBA), C57BL/6J (C57), BALB/cByJ (BALB), and WB/ReJ (WB), previously used to study age-related hearing loss, were evaluated serially as a function of age with 2f(1)-f(2) distortion-product otoacoustic emissions (DPOAEs). DPOAE levels in response to equilevel primary tones for geometric-mean (GM) frequencies from 5.6 to 48.5 kHz were recorded systematically as DP-grams and response/growth or input/output (I/O) functions at monthly intervals from about 2 to 15 months of age. Over the approximate 13-month measurement period, CBAs showed robust and unchanged DPOAEs for all tested frequencies, while BALBs, C57s, and WBs showed strain-specific, age-related decreases in DPOAEs that progressed systematically from the high to low frequencies. Specifically, for the youngest WBs at 2 months of age, no DPOAEs were recordable for GM frequencies > or = 32 kHz, while C57s and BALBs reached the identical stage of cochlear dysfunction by 5 and 8 months, respectively. The differential decline in DPOAE activity shown for WB, C57, and BALB mice supports the notion that they represent unique animal models of age-related changes in cochlear function. In contrast, the unchanging DPOAEs for CBAs over the same time period indicate that this strain makes an effective control for normal cochlear function in the mouse, at least, up to 15 months of age.     

Electrophysiological effects of the clinically used local anesthetics lidocaine,lidocaine-prilocaine and phenol on the rat's inner ear

Summary Local anesthetics, even if applied to the outer ear canal, may still enter the middle ear, running the risk of penetrating the round window. To elucidate the effect of certain topical anesthetics on the inner ear, the round window niche in the laboratory rat's middle ear was exposed separately to lidocaine, lidocaine-prilocaine and phenol. Auditory brain-stem responses (ABR) were recorded at 2, 4, 6, 8, 12, 16, 20, and 31.5 kHz before the application, and 24 h, 3 weeks, 2 months and 6 months after exposure. After terminating the 6-month ABR measurements, the animals were sacrificed and the temporal bones fixed and decalcified for light microscopic analysis. All three drugs affected the ABR thresholds and the cochlear morphology with a pattern characteristic for each drug. At 24 h, all three substances caused severe impairment of ABR thresholds, followed by a period of restitution lasting up to 2 months. Even 6 months after exposure, the ABR thresholds at and above 12 kHz were impaired, as compared with the pre-treatment level, for all substances tested. In the lower frequencies the original ABR threshold was reached in the order: (1) lidocaine, (2) lidocaine-prilocaine, (3) phenol. The cochlear structures were unaffected by lidocaine, whereas lidocaine-prilocaine and phenol caused morphological damage which was most pronounced after exposure to phenol. The heterogeneity of the changes in the ABR thresholds suggests differences in the mechanism of action of each type of local anesthetic investigated. The effects following lidocaine were transient. However, clinicians must be aware of the ototoxic potential of both lidocaine and phenol.     

Utility of auditory steady-state and brainstem responses in age-related hearing loss in rats

Conclusions: The results support the idea that auditory steady-state response (ASSR) is a more accurate test for studying age-related hearing loss (ARHL) in Sprague-Dawley rats. Differences in the rat middle ear may explain the variations of the click properties, with a displacement of the energy toward the 8 and 10 kHz frequencies compared with humans. Objectives: The purpose of this study was to evaluate ARHL in older and younger Sprague-Dawley rats using auditory clicks and tone burst with auditory brainstem response (ABR), in addition to ASSR. Methods: This was a prospective cohort study with 50 animals divided into 5 groups based on their age in months. A total of 100 registers were elicited from each one of the 3 auditory measurements systems in an electrically shielded, double-walled, sound-treated cabin. Nine frequencies, from 0.5 to 16 kHz were analyzed with the auditory steady-state response and compared with the results elicited by the clicks and tone-burst ABR. Results: Comparisons between the different frequencies showed lower thresholds in those frequencies below 2 kHz, independently of their age in months. The ARHL was detected by each one of the three auditory measurement systems, but with lower thresholds with the ASSR test. Finally, auditory clicks showed better correlations with 8 and 10 kHz elicited by ASSR, which was different to what was expected, based on human studies.     

Mechanisms of hearing loss resulting from middle-ear fluid

Fluid in the middle ear, a defining feature of otitis media with effusion (OME), is commonly associated with a 20- to 30-dB conductive hearing loss. The effects and relative importance of various mechanisms leading to conductive hearing loss were investigated in a human temporal bone preparation. Umbo velocity in response to ear-canal sound was measured with a laser vibrometer while saline and silicone fluids of viscosity 5-12,000 cSt were introduced into the middle ear to contact part or all of the tympanic membrane (TM) and fill part or all of the middle ear. At low frequencies, reductions in umbo velocity (deltaVU) of up to 25 dB depended on the percentage of the original middle-ear air space that remained air-filled, which suggests that the primary mechanism in hearing loss at low frequencies is a reduction of the admittance of the middle-ear air space due to displacement of air with fluid. At higher frequencies, deltaVU (of up to 35 dB) depended on the percentage of the TM contacted by fluid, which suggests that the primary mechanism at high frequencies is an increase in tympanic membrane mass by entrained fluid. The viscosity of the fluid had no significant effect on umbo velocity. deltaVU for the fluid-filled middle ear matched hearing losses reported in patients whose middle ear was believed to be completely filled with fluid. The difference between deltaVU for a partly-filled middle ear and hearing losses reported in patients whose middle ear was believed to be incompletely fluid-filled is consistent with the reported effect of middle-ear underpressure (commonly seen in OME) on umbo velocity. Small amounts of air in the middle ear are sufficient to facilitate umbo motion at low frequencies.     

Comparison between audiometric and ABR thresholds in children. Contradictory findings

The aim of the study was to predict hearing level thresholds with click-evoked ABR and to study the residual hearing when ABR was absent. In 85 hearing-impaired children, the conclusive pure-tone hearing level thresholds are reported. The exclusion criterion used was deteriorating hearing loss. The Jewett V-wave was identified in 48.2% of the subjects and was bilaterally absent in 51.8%. The correlation between ABR and PTA (2–4 kHz) thresholds was significant ( P <0.01). Audiometrically, 65.9% of the children with no response on ABR had hearing, and in 34.5% of these, the hearing loss was sloping. The median PTA (2–4 kHz) was 102 dB and the range from 65 to 120 dB. The accuracy of ABR is reasonably ineffective, because it overestimates the hearing loss in moderate and severe impairments. The absence of ABR indicates a significant hearing loss, but PTAs (2–4 kHz) as good as 65 dB were still found. Thus, a lack of response to click stimuli does not directly suggest none-viable residual hearing.     

Variability in genetically induced age-related impairment of auditory brainstem response thresholds

In genetically induced hearing impairment or deafness, the recessive mode of inheritance is by far the most common, but it has seldom been feasible to document audiological aberrations. In this study, auditory brainstem response (ABR) thresholds were analysed in groups of 10 heterozygote jerker (je/+) mice each, at ages of 3, 6 and 9 months in the frequency range 2-31.5 kHz. The animals were thereafter regularly tested up to a final age of 12 months. Forty age-related CBA/CBA mice were used as controls. The individual ABR thresholds in 3-, 6-, 9- and 12-month-old CBA/CBA mice were very similar, as also were those in 3- and 6-month-old je/+ mice (mean values within the normal range). In contrast, at 9 months--and even more so at 12 months--all je/+ animals showed large individual variations, with ABR thresholds varying randomly from near-normal to profound impairment. The wide individual spread of ABR thresholds in old je/+ animals was interpreted as reflecting the expression of a random influence of recessive jerker vis-à-vis the wild type of gene.     

The influence of age on the results of stapedectomy

Summary In a retrospective study, we investigated the results of 384 stapedectomies performed between 1962 and 1989. The purpose was to determine the possible influence of age on the postoperative functional result. The operative technique uniformly consisted of a total stapedectomy, seal of the oval window with perichondrium and replacement of the stapes by a free tragal cartilage graft. The audiometric data at 0.5, 1, 2, and 4 kHz were compared. The patients were divided into five groups based upon chronological age: under 30, 30–40, 41–50, 51–60, over 60 years. Although the preoperative airbone gap (ABG) increased with age at all frequencies, and thus the chance for surgery to improve the ABG, the youngest group showed the best improvement in ABGG (P<0.05). Using a technique with total removal of the footplate, bone conduction thresholds improved in the frequencies up to 2 kHz. At 4 kHz, they deteriorated in the four oldest groups. The greatest improvement in bone conduction thresholds occurred in the youngest group of patients (P<0.05), with a parallel decline in age and postoperative results occurring. The causes of these differences are not yet clear, although spontaneous recovery and greater resistance to operative trauma in the younger age groups might be of influence.Presented at the 87th French Congress on Otorhinolaryugology, Head and Neck Surgery, 8–11 October 1990, Paris, France     

Effects of exposing C57BL/6J mice to high- and low-frequency augmented acoustic environments: auditory brainstem response thresholds, cytocochleograms, anterior cochlear nucleus morphology and the role of gonadal hormones

Gonadectomized and intact adult C57BL/6J (B6) mice of both sexes were exposed for 12h nightly to an augmented acoustic environment (AAE): repetitive bursts of a 70dB SPL noise band. The high-frequency AAE (HAAE) was a half-octave band centered at 20kHz; the low-frequency AAE (LAAE) was a 2-8kHz band. The effects of sex, gonadectomy, and AAE treatment on genetic progressive hearing loss (a trait of B6 mice) were evaluated by obtaining auditory brainstem response (ABR) thresholds at ages 3-, 6-, and 9-months. At 9-months of age, hair cell counts (cytocochleograms) were obtained, and morphometric measures of the anteroventral cochlear nucleus (AVCN) were obtained. LAAE treatment caused elevation in ABR thresholds (8-24kHz), with the highest thresholds occurring in intact females. LAAE treatment caused some loss of outer hair cells in the basal half of the cochlea (in addition to losses normally occurring in B6 mice), with intact females losing more cells than intact males. The loss of AVCN neurons and shrinkage of tissue volume that typically occur in 9-month-old B6 mice was lessened by LAAE treatment in intact (but not gonadectomized) male mice, whereas the degenerative changes were exacerbated in intact (but not gonadectomized) females. These LAAE effects were prominent in, but not restricted to, the tonotopic low-frequency (ventral) AVCN. HAAE treatment resulted in some loss of neurons in the high-frequency (dorsal) AVCN. In general, LAAE treatment plus male gonadal hormones (intact males) had an ameliorative effect whereas HAAE or LAAE treatment plus ovarian hormones (intact females) had a negative effect on age-related changes in the B6 auditory system.