Cochlea ; metabolism ; Deafness ; genetics ; Humans ; Mutation

Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.
Mice ; Animals ; Transcriptome ; Aging/metabolism* ; Cochlea ; Stria Vascularis ; Presbycusis

OBJECTIVE: To study the expression of nuclear factor kappa B p65 in hyperlipemia model of mice, and the relationship between hyperlipemia and deaf. METHOD: Twenty mice were divided into two group. The hyperlipemia diet group was established in ten mice,and the normal diet group was served as normal control. Six weeks later, immunohistostaining was used to detected the express of NF-kappa B p65 in all mouse cochlear. ABR threshold was obtained from both normal group and hyperlipemia group. RESULT: Immunoreactivity NF-kappa B p65 in mouse cochlea of hyperlipemia was localized in the organ of Corti, tectorial membrane, stria vascularis, spiral ligament, spiral ganglion and nerve fibers. The NF-kappa B p65 expression was markedly increased in mouse cochlea of hyperlipemia ABR threshold was significant difference between hyperlipemia group mice and control group mice (P < 0.01). CONCLUSION The expression of NF-kappa B p65 in mouse cochlea can be induced by hyperlipemia. And ABR threshold increased in hyperlipemia group mice. This shows that hyperlipidemia can damage acouesthesia of mice.
Animals ; Cochlea ; metabolism ; Disease Models, Animal ; Hyperlipidemias ; metabolism ; Mice ; Mice, Inbred Strains ; Transcription Factor RelA ; metabolism

Animals ; Cochlea ; growth & development ; metabolism ; Female ; Guinea Pigs ; Male ; Nerve Growth Factor ; metabolism

Recent studies have revealed great functional and structural heterogeneity in the ribbon-type synapses at the basolateral pole of the isopotential inner hair cell (IHC). This feature is believed to be critical for audition over a wide dynamic range, but whether the spatial gradient of ribbon morphology is fine-tuned in each IHC and how the mitochondrial network is organized to meet local energy demands of synaptic transmission remain unclear. By means of three-dimensional electron microscopy and artificial intelligence-based algorithms, we demonstrated the cell-wide structural quantification of ribbons and mitochondria in mature mid-cochlear IHCs of mice. We found that adjacent IHCs in staggered pairs differ substantially in cell body shape and ribbon morphology gradient as well as mitochondrial organization. Moreover, our analysis argues for a location-specific arrangement of correlated ribbon and mitochondrial function at the basolateral IHC pole.
Animals ; Artificial Intelligence ; Cochlea/metabolism* ; Hair Cells, Auditory, Inner ; Mice ; Mitochondria ; Synapses/metabolism*

OBJECTIVETo study the interaction among aquaporin1 (AQP), aquaporin2 (AQP2) and antisecretory factor( AF) , and their expression in the rat inner ear for furthur understanding of Meniere' s disease.

METHODSInner ear tissue section of six healthy male Sprague-Dawley rats was performed and Envision immunochemical staining was applied to detect the expression of AF, AQP1 and AQP2 in the rat inner ear. Vestibular and cochlear tissues of twenty healthy male Sprague-Dawley rats were dissected. Coimmunoprecipitation and Western Blot were used to specifically immunoprecipitate AF protein in the vestibular and cochlear tissues with monoclonal antibodies against AQP1 and polyclonal antibodies antibodies against AQP2 to detect the above precipitate with specific antibodies against AF.

RESULTS(1) AF was widely distributed in the inner ear, such as marginal cells of stria vascularis , five classes of spiral ligament fibrocyte , Reissner's membrane, basilar membrane, ampullar crest and so on with mild or moderate staining. In addition, round membrane was moderately or markedly stained. Positive immunostaining was found in the cochlear spiral ganglion, vestibular nerve and cochlear nerve. AQP1 was distributed in the intermediate cells in stria vascularis, type III fibrocyte of spiral ligament, basilar membrane and round membrane with moderate to marked degree of immunostaining intensity. AQP2 was mainly localized to the type II, IV, and V fibrocyte of spiral ligament, with moderate to marked degree of immunostaining intensity, round membrane was weakly stained. (2) No band was observed in the control and a single immunoreactive band of 60 000 was observed, which was equal to the molecular mass of AF.

CONCLUSIONS(1) AF, AQP1 and AQP2 have its individual specific localization in the rat inner ear, which was close to the parts of endolymph, so regulating water of the endolymph may be possible. (2) The range of localization of AF overlapped the distribution of AQP1 and AQP2. The results showed the existence of AF protein in the immunoprecipitate using co-immunoprecipitation combined with Western Blot. It suggested that the interaction between AQP1, AQP2 and AF might be possible.

Animals ; Aquaporin 1 ; metabolism ; Aquaporin 2 ; metabolism ; Cochlea ; metabolism ; Ear, Inner ; metabolism ; Male ; Neuropeptides ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the expression of aquaporin 1 (AQP1) in cochlea and endolymphatic sac of guinea pig of two types of animal model of endolymphatic hydrops.

METHODSThirty guinea pigs were divided into three groups at random: surgery group; aldosterone group and control group. Each group included 10 animals. Surgical endolymphatic sac obstruction or aldosterone intraperitoneal injection was used to build the animal models of endolymphatic hydrops. Immunohistochemistry and western blot were used to examine the expression of AQP1 in cochlea and endolymphatic sac of animal models. Image processing soft (Image Tool) was used to do the semiquantitative analysis.

RESULTSMiddle to high grade endolymphatic hydrops were found in surgery group. It was most significant in the apical coil, and lessened from the apical coil to the basal coil. Low to middle expression grade in endolymphatic hydrops was found in aldosterone group. Most of them were found in the basal coil. The positions of AQP1 expression in two animal models of endolymphatic hydrops were identical with the control group. In cochlea, no difference of AQP1 expression was found in the surgery and control group (t = 0.718 , P > 0.05) , but the expression of AQP1 was down regulated in the cochlea of aldosterone group (t = 6.609, P < 0.01) while the expressions of AQP1 in endolymphatic sac of aldosterone and control group were no difference between them (t = 0.998, P > 0.05). The quantization of AQP1 protein in the lateral wall of cochlea of aldosterone group was lower than that of control group (t = 13.626 , P < 0.01).

CONCLUSIONSThe expression of AQP1 is no change in surgery and control group, but decreased in aldosterone group. The expression of AQP1 may be regulated by the ionic concentration in inner ear of guinea pig.

Animals ; Aquaporin 1 ; metabolism ; Cochlea ; metabolism ; Disease Models, Animal ; Endolymphatic Hydrops ; metabolism ; Endolymphatic Sac ; metabolism ; Guinea Pigs

OBJECTIVE: To observe the changes of GABA and GABAergic neurons in rat inferior colliculus following unilateral cochlear damage and explore the function and significance of GABA in reorganization of auditory center after deafferentation. METHOD: Twenty sprague dawley rats were divided into four groups randomly. The technique of direct anti-GABA immunocytochemistry (SP) was used in this study. The quantity of GABA was measured by 835-50 type Amino Acid Automatism Analyzer and compared at one week, two weeks and one month after unilateral cochlear ablation, respectively. RESULT: Compared with controlled groups, the quantity levels of GABA decreased and the number of GABAergic neurons also reduced one week after unilateral cochlear damage and there was a significant difference in GABA between two groups( P <0. 05); after one month, the quantity of GABA and the number of GABAergic neurons almost reached the normal level, the differences were no significant. CONCLUSION The dynamic change of GABA in rat inferior colliculus reflected the neuronal activity, which implied that GABA may play an important role in reorganization of auditory center after unilateral cochlear damage.
Animals ; Cochlea ; metabolism ; pathology ; Inferior Colliculi ; metabolism ; Neurons ; metabolism ; Rats ; Rats, Sprague-Dawley ; gamma-Aminobutyric Acid ; metabolism

In mammals, the piezoelectric protein, Prestin, endows the outer hair cells (OHCs) with electromotility (eM), which confers the capacity to change cellular length in response to alterations in membrane potential. Together with basilar membrane resonance and possible stereociliary motility, Prestin-based OHC eM lays the foundation for enhancing cochlear sensitivity and frequency selectivity. However, it remains debatable whether Prestin contributes to ultrahigh-frequency hearing due to the intrinsic nature of the cell's low-pass features. The low-pass property of mouse OHC eM is based on the finding that eM magnitude dissipates within the frequency bandwidth of human speech. In this study, we examined the role of Prestin in sensing broad-range frequencies (4-80 kHz) in mice that use ultrasonic hearing and vocalization (to >100 kHz) for social communication. The audiometric measurements in mice showed that ablation of Prestin did not abolish hearing at frequencies >40 kHz. Acoustic associative behavior tests confirmed that Prestin-knockout mice can learn ultrahigh-frequency sound-coupled tasks, similar to control mice. Ex vivo cochlear Ca²⁺ imaging experiments demonstrated that without Prestin, the OHCs still exhibit ultrahigh-frequency transduction, which in contrast, can be abolished by a universal cation channel blocker, Gadolinium. In vivo salicylate treatment disrupts hearing at frequencies <40 kHz but not ultrahigh-frequency hearing. By pharmacogenetic manipulation, we showed that specific ablation of the OHCs largely abolished hearing at frequencies >40 kHz. These findings demonstrate that cochlear OHCs are the target cells that support ultrahigh-frequency transduction, which does not require Prestin.
Animals ; Cochlea/metabolism* ; Hair Cells, Auditory, Outer/metabolism* ; Hearing ; Humans ; Mammals/metabolism* ; Mice ; Mice, Knockout ; Molecular Motor Proteins/metabolism*

Animals ; Arteries ; metabolism ; Cochlea ; blood supply ; Cystathionine gamma-Lyase ; genetics ; Rats ; Rats, Sprague-Dawley