[Changes of BK(Ca) on vascular striaepericytes of D-galactose-induced aging model in guinea pigs].

Objective: The aging model of guinea pigs induced by D-galactose was set up to investigate the changes of BK(Ca) expression and function on cochlear pericytes and their relationship with age-related hearing loss. Methods: Thirty healthy 8-week-old guinea pigs were randomly divided into three groups, with 10 in each group: D-galactose aging model group, subcutaneous injection of D-galactose (500 mg/kg) daily for 6 weeks; saline control group, the same amount of saline was injected into the neck of the aging model group for 6 weeks; the blank control group, no treatment was performed. The threshold of auditory brainstem response (ABR) was detected. The content of BK(Ca) in the perivascular cells of the guinea pig cochlear cells was detected by immunofluorescence technique. The changes of peripheral current density and BK(Ca) current were detected by patch clamp technique. The data were analyzed by GraphPad Prism software. Results: Compared with the saline group and the control group, the ABR threshold and the amplitude of the wave I were significantly decreased in the aging model group, and the difference was statistically significant (P<0.01). Compared with the control group, the expression of BK(Ca) in the vascular pericytes of guinea pigs in the aging model group was significantly reduced (1.00±0.08 vs 0.27±0.03,the difference was statistically significant P<0.01), and the cell current density and BK(Ca) net current value were also significantly reduced with statistically significant (P<0.01). Conclusions: D-galactose can successfully induce guinea pig aging model, in which BK(Ca) expression decreases and net current value decreases in pericytes of cochlear striavascularis, and changes in BK(Ca) expression and function may be related to age-related hearing loss.

The role of sodium hydrosulfide in attenuating the aging process via PI3K/AKT and CaMKKß/AMPK pathways.

Age-related dysfunction of the central auditory system, known as central presbycusis, is characterized by defects in speech perception and sound localization. It is important to determine the pathogenesis of central presbycusis in order to explore a feasible and effective intervention method. Recent work has provided fascinating insight into the beneficial function of H2S on oxidative stress and stress-related disease. In this study, we investigated the pathogenesis of central presbycusis and tried to explore the mechanism of H2S action on different aspects of aging by utilizing a mimetic aging rat and senescent cellular model. Our results indicate that NaHS decreased oxidative stress and apoptosis levels in an aging model via CaMKKß and PI3K/AKT signaling pathways. Moreover, we found that NaHS restored the decreased activity of antioxidants such as GSH, SOD and CAT in the aging model in vivo and in vitro by regulating CaMKKß and PI3K/AKT. Mitochondria function was preserved by NaHS, as indicated by the following: DNA POLG and OGG-1, the base excision repair enzymes in mitochondrial, were upregulated; OXPHOS activity was downregulated; mitochondrial membrane potential was restored; ATP production was increased; and mtDNA damage, indicated by the common deletion (CD), declined. These effects were also achieved by activating CaMKKß/AMPK and PI3K/AKT signaling pathways. Lastly, protein homeostasis, indicated by HSP90 alpha, was strengthened by NaHS via CaMKKß and PI3K/AKT. Our findings demonstrate that the ability to resist oxidative stress and mitochondria function are both decreased as aging developed; however, NaHS, a novel free radical scavenger and mitochondrial protective agent, precludes the process of oxidative damage by activating CaMKKß and PI3K/AKT. This study might provide a therapeutic target for aging and age-related disease.

Hormone replacement therapy diminishes hearing in peri-menopausal mice.

We recently discovered that progestin in hormone replacement therapy (HRT) for post-menopausal women has detrimental effects on the ear and central auditory system [Guimaraes, P., Frisina, S.T., Mapes, F., Tadros, S.F., Frisina, D.R., Frisina, R.D., 2006. Progestin negatively affects hearing in aged women. Proc. Natl. Acad. Sci. - PNAS 103, 14246-14249]. To start determining the generality and neural bases of these human findings, the present study examined the effects of combination HRT (estrogen+progestin) and estrogen alone on hearing in peri-menopausal mice. Specifically, auditory brainstem responses (ABRs-sensitivity of the auditory system) and distortion-product otoacoustic emissions (DPOAEs-cochlear outer hair cell system) were employed. Middle age female CBA mice received either a time-release, subcutaneous implanted pellet of estrogen+progestin, estrogen alone, or placebo. Longitudinal comparisons of ABR threshold data obtained at 4 months of treatment revealed statistically significant declines in auditory sensitivity over time for the combined estrogen+progestin treatment group, with the estrogen only group revealing milder changes at 3, 6 and 32 kHz. DPOAE testing revealed statistically significant differences for the estrogen+progestin treatment group in the high and middle frequency ranges (15-29 and 30-45 kHz) after as early as 2 months of treatment (p<0.01 and p<0.001, respectively). Statistically significant changes were also seen at 4 months of treatment across all frequencies for the combined HRT group. These data suggest that estrogen+progestin HRT therapy of 4 months duration impairs outer hair cell functioning and overall auditory sensitivity. These findings indicate that estrogen+progestin HRT may actually accelerate age-related hearing loss, relative to estrogen monotherapy; findings that are consistent with the clinical hearing loss observed in aging women that have taken combination HRT.

Amalgam dental fillings and hearing loss.

In this study we investigated the effects of amalgam dental fillings on auditory thresholds. Participants (n=39) were non-smoking women age 40 to 45. Regression and correlation analyses were performed between auditory thresholds, measured from 0.25 to 16 kHz, and the number/surface area of dental fillings, using the ASHA criteria for ototoxic change as a reference for comparison. No significant correlation (p>0.05) was found between composite (non-amalgam) filling or drilling data and auditory thresholds. However, there was a significant positive linear correlation between amalgam filling data and auditory thresholds at 8, 11.2, 12.5, 14, and 16 kHz. The strongest association (r=0.587, n=39, p<.001, r(2)=0.345) was at 14 kHz, where each additional amalgam filling was associated with a 2.4 dB decline in hearing threshold (95% confidence interval [CI], 1.3-3.5 dB). The results suggest an association between more amalgam fillings and poorer thresholds at higher frequencies, which could contribute to presbyacusis in developed countries. This provides further argument for the use of amalgams to be phased out where suitable alternatives exist.

[Detection of hearing threshold and polymorphic molecular marker analysis of guinea pigs of mimetic aging].

OBJECTIVE: To explore the establishment of the mimetic aging effect in guinea pigs induced by D-galactose, and to detect the biological indicatrix associated with hearing loss and provide a new tool for molecular pathogenesis of hearing loss. METHODS: Total of 51 guinea pigs were randomly divided into three groups: group A (model aging group, n = 25), which were injected with D-galactose (200 mgxkg(-1)xd(-1)) by intra peritoneum for 6 weeks, group B (model control group, n = 18), which were given the same amount of saline only, and group C (vacant group, n = 15) were not treated. Then, The guinea pigs in group A and B were exposed in noise for 8 days, 8 hours once a day. Auditory brainstem response (ABR) was used to test the hearing threshold of guinea pigs thrice, first before the drug administered, then after 6 weeks the drug used, third after noise exposure. And colorimetry was used to analyze the activity of superoxide dismutase (SOD) and malon dialdehyde (MDA) in brain and liver tissue. The DNA of inner ear tissue was harvested and amplified fragment length polymorphism (AFLP) was used to detect the differential polymorphic markers. RESULTS: After injection, there was no significant difference in elevation of ABR threshold between the group A and group B (t = 1.14, P > 0.05). However, exposure of noise later, elevation in ABR threshold of (22.97 +/- 10.56) dB peSPL was observed in group A, and (14.16 +/- 7.36) dB peSPL in group B. The was significant difference in variation of hearing threshold between group A and group B (t = 2.78, P < 0.05). The activity of SOD in brain and liver tissue in group A was lower than that in group B. the level of MDA was opposite between group A and group B. The difference between group A and group B was significant (P < 0.01). A differential polymorphic marker was observed by AFLP. CONCLUSIONS: The mimetic aging effect of the guinea pigs can be induced by D-galactose, and this model can not directly induce the hearing loss. The differential polymorphic marker possibly act as a predisposing factor which can greatly enhance the sensitivity of the ear to the noise.

Correlations between presbyacusis and extrinsic noxious factors.

As part of the longitudinal gerontological and geriatric population study of 70-year-olds in Göteborg, Sweden, the possible correlation between presbyacusis and extrinsic factors affecting health in elderly persons was investigated. Participants from one cohort (F 01) were studied longitudinally at ages 70, 75, 79 and 85 years, and from another cohort (F 06) at age 70 years. A weak correlation between hearing loss and smoking, alcohol abuse and head trauma was found for men and between hearing loss and intake of pharmaceutical agents (especially salicylates) for women.