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PubMed1997

Comparison of tyrosine hydroxylase immunoreactivity in cochleas of chinchilla and guinea pig.

OBJECTIVE: To investigate the distribution of the tyrosine hydroxylase (TH) immunoreactivity in the cochleas of chinchilla and compare it with guinea pig. METHODS: Ten healthy chinchillas and six healthy guinea pigs were used in this study. The surface preparation of cochleas were obtained by microdissection. The TH-like immunoreactivity on the surface preparation as examined by the avidin and biotinylated horseradish peroxidase macromolecular complex (ABC) technique and investigated with light microscopy. RESULTS: TH-like immunoreactivity was seen in the region from modiolus to the habenula perforata. There are two different groups of fibers in this area, one is blood vessel dependent, the other is a blood vessel independent system. No TH-like immunoreactivity was present in the inner spiral bundle (ISB) and the tunnel spiral bundle (TSB) regions in chinchilla cochleas. TH-like immunoreactivity was found in the region from modiolus to the habenula perforata and the ISB and TSB regions in the organ of corti (OC) in guinea pig cochleas. CONCLUSIONS: The presence of TH-immunoreactivity on the cochlea of chinchilla and guinea pig is different. TH-like immunoreactivity on chinchilla cochlea was involved only in the fibers corresponding to the sympathetic fibers on cochlea of guinea pig. No fibers corresponding to the dopaminergic olivocochlear lateral efferent system of guinea pig were found in ISB and TSB within the OC in chinchilla.

Adrenergic Fibers↗

PubMed2003

Cochlear implantation in prelingually deaf children with ossified cochleae.

OBJECTIVE: To evaluate the effects that degree of cochlear ossification has on performance of prelingually deafened children who receive cochlear implants. STUDY DESIGN: A matched-pairs analysis comparing speech perception results obtained 6 and 24 months after implant by children with ossified and nonossified cochleae. Additionally, long-term performance was evaluated in patients with follow-up periods longer than 24 months. Comparisons were also performed within the ossified cochleae group to determine if degree of cochlear ossification and surgical technique affected outcome with the cochlear implant. SETTING Large cochlear implant program in an academic tertiary care medical center. PATIENTS: Twenty-one pairs of prelingually deaf children with and without cochlear ossification. Meningitis was the etiology of hearing loss in children with ossified cochleae. The control group had nonmeningitic etiology for the hearing loss. INTERVENTIONS: Multichannel cochlear implantation and routine postoperative auditory rehabilitation and performance evaluation. MAIN OUTCOME MEASURES: Speech perception category ratings based on scores obtained on a battery of closed- and open-set speech recognition tests 6 and 24 months after implant. Longer follow-up period is also reported. RESULTS: As a group, children with cochlear ossification showed significant improvement in their speech perception abilities 6 and 24 months after implant. Children with cochlear ossification performed at a significantly lower speech perception category than a group of matched controls with nonossified cochleae at both the 6- and 24-month postimplant intervals. With longer implant use, open-set speech recognition was possible in some children with ossification. Within-group analysis of the children with ossified cochleae revealed that degree of ossification and surgical procedure used for implantation did not significantly affect outcome. CONCLUSIONS: Prelingually deafened children with postmeningitic hearing loss and ossified cochleae receive significant benefit from cochlear implants. Their performance is frequently poorer, however, than children with nonossified cochleae.

Case-Control Studies↗

PubMed1990

Effects of cochlea removal on GABAergic terminals in nucleus magnocellularis of the chicken.

The effects of unilateral cochlea removal on GABA-immunoreactive (GABA-I) terminals in nucleus magnocellularis (NM) of the chick were assessed by immunocytochemical (ICC) techniques. Posthatch chicks (5-8 days old) survived from 1-37 days following unilateral cochlea removal. In the ipsilateral NM, the density of GABA-I terminals appeared to increase relative to normal controls 10-37 days after cochlea removal. However, most of that increase could be attributed to a decrease in cell size, cell number, and volume of the nucleus as a result of deafferentation. In the contralateral NM, the density of GABA-I terminals decreased relative to the ipsilateral NM and to normal animals 1-21 days after cochlea removal. The number of GABA-I terminals per NM neuron also decreased in the contralateral NM while that in the ipsilateral NM was comparable to normal controls. To ascertain whether these changes represented changes in the number of terminals or in the amount of GABA contained within the terminals, we also examined these terminals using an antibody to glutamic acid decarboxylase (GAD), the biosynthetic enzyme for GABA. Following unilateral cochlea removal, there was no difference in the density of GAD-I terminals in NM between the two sides of the brain for any of the survival times. Similarly, bilateral cochlea removal had no discernible effect on the density of GABA-I terminals in NM. These data suggest that unilateral deafferentation may temporarily downregulate the biosynthesis of GABA in the contralateral NM.

Animals↗

PubMed1988

Prostaglandin synthesis by the cochlea.

The exogenous and endogenous syntheses of prostaglandins (PG's) by the cochlea of adult mongolian gerbils were studied in vitro. After incubation of the whole membraneous cochlea with [3H]-arachidonic acid (AA), syntheses of PGF2 alpha, 6-keto PGF1 alpha, PGE2, thromboxane (TX) P2 and PGD2 were evidenced in this order. The synthesis of radioactive PG's was almost completely inhibited by incubation with 10(-5) M indomethacin. No significant amounts of those PG's were detected by radioimmunoassay (RIA) in the cochlea obtained from animals killed by microwave irradiation at 5.0 kw for 0.8 sec. However, when the homogenate of the whole membraneous cochlea obtained from animals without microwave irradiation was incubated at 37 degrees C for 0-15 min, PGD2, PGE2, PGF2 alpha and 6-keto PGF1 alpha were found to be formed from endogenous AA in the cochlea by RIA. PG's were formed already at 0 time to considerable level (PGD2, PGF2 alpha and 6-keto PGF1 alpha, 90-120 pg/cochlea; PGE2, 370 pg/cochlea), reached to the maximum level (PGD2, PGF2 alpha and 6-keto PGF1 alpha, 170-200 pg/cochlea; PGE2, 500 pg/cochlea) at a 5-min incubation, and then gradually decreased. On the other hand, the amount of TXB2 was lower than the detection limit by RIA (less than 50 pg/cochlea) even after the incubation. The cochlea was dissected into three parts: organ of Corti + modiolus (OC + M), lateral wall (LW), and cochlear nerve (CN), and then PG's formed by these tissues were determined after a 5-min incubation of the homogenates. In the CN and OC + M, PGE2 was the major PG (100 and 160 pg/tissue, respectively), and the amounts of PGD2, PGF2 alpha and 6-keto PGF1 alpha were about 1/3 of those of PGE2. In the LW, the amounts of PGD2, PGE2, PGF2 alpha and 6-keto PGF1 alpha were about the same level (70-100 pg/LW).

6-Ketoprostaglandin F1 alpha↗

PubMed1984

Computerized reconstruction of the regional blood flow in the rodent cochlea.

The regional blood flow in the cochlea has been studied by mapping the distribution of microspheres in 22 micron thick serial sections of plastic embedded rat and rabbit cochleas. Using a computer-assisted reconstruction technique, a graphic display of the microspheres in each cochlea is obtained. From this display, microspheres may be counted and their distribution may be observed both in relation to the different vascular areas and with respect to the length of the cochlea. This technique, coupled with quantitation of the microspheres in a reference blood sample, offers a method for calculating total and regional cochlear blood flow using non-radioactive microspheres. In addition, this technique allows analysis of blood flow patterns with respect to the different capillary beds along the length of the cochlea. Thus it may be possible to determine if regional blood flow displays a longitudinal gradient, as do other functional, morphologic and biochemical characteristics of the cochlea.

Animals↗

PubMed1990

Blood flow changes in chicken brain stem auditory nuclei following cochlea removal.

Cochlea removal results in rapid and persistent metabolic and morphological changes in avian brain stem auditory nuclei. Because such changes in the central nervous system are often associated with changes in local blood flow, we examined blood flow in second-order auditory nucleus magnocellularis (NM) and third-order nucleus laminaris (NL). The diffusible tracer [14C]-iodoantipyrine was infused intravenously into 20- to 26-day-old chickens either 30 min or 6 h after unilateral cochlea removal. This tracer rapidly equilibrates between blood and tissue in proportion to local blood flow. Unoperated animals served as controls. Thirty seconds after tracer infusion, brains were removed and frozen. Cryostat sections were prepared for quantitative film autoradiography. Blood flow in normal and deafferented areas within NM and NL was compared. Nucleus magnocellularis receives its only excitatory input from the ipsilateral cochlea via the eighth nerve. Axons from NM bifurcate and project to the ipsilateral dorsal dendritic region of NL (NLd) and the contralateral ventral dendritic region of NL (NLv). Thirty minutes after cochlea removal, blood flow in ipsilateral NM decreases by 30%. This decrease persists at 6 hours. Blood flow in NL does not change in accordance with the pattern of afferent input from NM. Rather, blood flow in NLd and NLv ipsilateral to cochlea removal is significantly decreased 6 h post lesion. These results are in contrast to the pattern of morphological and metabolic changes observed in NL after cochlea removal.

Animals↗

PubMed1991

Monoclonal antibodies to inner ear antigens: I. Antigens expressed by supporting cells of the guinea pig cochlea.

Murine monoclonal antibodies against guinea pig cochlear epithelium were generated with the goal of identifying cochlea-specific antigens and elucidating their function. To compensate for the limited amount of cochlear tissue, intrasplenic immunization was used. Hybridoma supernatants were screened by ELISA for antibody production and for binding to homogenates from cochlea, liver, lung, kidney and brain. Hybrids producing antibody to cochlea were subcloned and tested immunocytochemically against frozen sections and surface preparations of paraformaldehyde-fixed cochlear tissue. KHRI-1, a low titer IgM antibody stained only Hensen cells. KHRI-2, also an IgM antibody, stained tectorial membrane, cells of the spiral limbus, cells bordering the space of Nuel, Hensen cells and the root cells of the spiral prominence. KHRI-3, an IgG1 antibody, stained the phalangeal processes of outer pillar cells and the apical portion of phalangeal processes of Deiters' cells in a distinctive wine goblet pattern on surface preparations. KHRI-3 antibody also reacted with peripheral nerves and pia mater of brain in unfixed frozen sections but the antigenic site was not stable to fixation in contrast to the epitope detected in the cochlea. In Western blots of detergent extracts from cochlea KHRI-3 stained a broad tissue-specific band of Mr 70-75 kDa; a narrower band of Mr 68-70 kDa was identified by KHRI-3 in extracts of tongue and brain. KHRI-1 and KHRI-2 did not detect any proteins in Western blots. The monoclonal antibodies KHRI-1, -2, and -3 which define epitopes expressed by discrete populations of supporting cells in the inner ear should be useful in characterizing the nature and function of cellular structures in the cochlea.

Animals↗

PubMed1995

Detection and quantification of endolymphatic hydrops in the guinea pig cochlea by magnetic resonance microscopy.

Three-dimensional magnetic resonance microscopy (MRM) was used to study normal and hydropic cochleae of the guinea pig. With this technique consecutive serial slices representing the entire volume of isolated, fixed cochleae were obtained. The voxels (volume elements) making up the contiguous slices were isotropic (25 microns 3) and in each slice the boundaries of scala media, including the position of Reissner's membrane, were clearly delineated. Three-dimensional reconstructions of the endolymphatic and perilymphatic scale were generated. Custom software was developed to quantify cross-sectional area (CSA) of all scalae. In the normal cochlea all 3 scalae, including scala media, showed a gradual decrease in CSA from base to apex. Marked differences existed between our findings and previously reported cochlear dimensions, especially for the perilymphatic scalae in the basal turn. In hydropic cochleae the scala media was enlarged to a varying extent in different turns and marked changes in the degree of distension of Reissner's membrane occurred along the cochlea. MRM and subsequent computer analysis of the isotropic data provide excellent methods for imaging and quantifying the fluid spaces of normal and hydropic cochleae.

Animals↗

PubMed1995

Regenerated nerve fibers in the noise-damaged chinchilla cochlea are not efferent.

Nerve-fiber regeneration in the chinchilla cochlea following a traumatic noise exposure was systematically described by Bohne and Harding (1992). However, their study did not determine the origin of the regenerated nerve fibers (RNFs). In the present study, 23 chinchillas were exposed for 12 h to a 0.5 kHz octave band of noise at 120 dB SPL. After a 3-month or 1-year recovery period, their right cochleas were incubated to demonstrate acetylcholinesterase (AChE) activity and then briefly counterstained with Neutral Red or OsO4. Their left cochleas were fixed with OsO4 and dissected using a combined organ of Corti (OC)/modiolus technique that preserved both structures for high-resolution microscopy. All cochleas were prepared as plastic-embedded flat preparations. Damage was located in the basal two-thirds of the cochlea and generally consisted of multiple lesions in the OC, often involving total degeneration of one or more OC segments (i.e., OC wipeouts). The OC wipeouts were separated from one another by areas which contained some identifiable cells of the OC (i.e., OC remnants). Most RNFs were found in OC wipeouts adjacent to OC remnants. In those animals (83%) with significant OC damage, 13 (100%) 3-month-recovery chinchillas had 1-96 RNFs while 6 (86%) 1-year-recovery chinchillas had 7-62 RNFs. In the AChE-stained cochleas, none of the RNFs were AChE-positive, but normal AChE-positive fibers were found in the undamaged apical turn. A variable number of surviving spiral ganglion cells was present in those regions of Rosenthal's canal that had originally innervated the missing hair cells in the OC wipeouts and remnants. It is concluded that RNFs are not part of the efferent cochlear system and therefore, most likely belong to the afferent system.

Acetylcholinesterase↗

PubMed2005

Expression patterns of connexin 29 (GJE1) in mouse and rat cochlea.

Multiple types of connexin (Cxs) products, including Cx26, Cx30, Cx31, and Cx43, are found by immunolabeling in the mature cochlea. The transcript of Cx29, a newly discovered member of Cx gene family, was also discovered in the cochlea by cDNA macroarray hybridization. However, the functional roles of Cx29 in the cochlea remain unclear. To elucidate whether the Cx29 gap junction protein epsilon 1, GJE1, is localized in the adult mouse and rat cochlea, we performed an immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) analysis. GJE1 was detected in the cochlea neurons, spiral limbus, spiral ligament, organ of Corti, and stria vascularis using IHC analysis. We also show that Cx29 mRNA is present in spiral limbus, spiral ligament, organ of Corti, stria vascularis, and lateral wall by the method of RT-PCR. Higher levels of Cx29 mRNA were found in spiral ligament and spiral limbus, whereas lower level in lateral wall. Our data first provide a comprehensive and detailed pattern of Cx29 gene expression in the mouse and rat cochlea. Knowledge of spatial distribution of Cx29 also allows the identification of candidate genes for deafness and provides important insight into mechanisms that lead to deafness due to mutations in Cx29 gene.

Animals↗

PubMed2005

Nuclear factor-kappa B nuclear translocation in the cochlea of mice following acoustic overstimulation.

There is increasing evidence to suggest that the expression of many molecules in the lateral wall of the cochlea plays an important role in noise-induced stress responses. In this study, activation of the nuclear transcription factor nuclear factor-kappa B (NF-kappaB) was investigated in the cochlea of mice treated with intense noise exposure (4 kHz, octave band, 124 dB, for 2 h). The present noise exposure led to remarkable auditory brainstem response threshold shifts and cochlear damage on surface preparations. To assess the effects of noise exposure on NF-kappaB/DNA binding activity in the cochlea, we prepared nuclear extracts from the cochlea at different time points after noise exposure and carried out an electrophoretic mobility shift assay using a probe specific to NF-kappaB. NF-kappaB/DNA binding was significantly enhanced in the cochlea 2-6 h after noise exposure and returned to basal levels after 12 h. Supershift analysis using antibodies against p65 and p50 proteins, which are components of NF-kappaB, demonstrated that enhancement of NF-kappaB/DNA binding was at least in part due to nuclear translocation of p65. An immunohistochemical study also showed that nuclear translocation of both p65 and p50 was observed in the lateral wall after noise exposure and that there may be a possible close association between p65 and enhanced inducible nitric oxide synthase expression. These results suggest that NF-kappaB may have a detrimental role in the response to acoustic overstimulation in the cochlea of mice.

Acoustic Stimulation↗

PubMed2004

Tracing neurotrophin-3 diffusion and uptake in the guinea pig cochlea.

Neurotrophin therapy in the cochlea can potentially slow or reverse the degeneration of the auditory nerve that occurs during progressive deafness. Studies were performed to trace the diffusion and uptake of neurotrophin-3 (NT-3) following infusion into the cochlea. NT-3 labeled with (125)I or coated onto fluorescent microspheres was introduced into the basal turn of normal hearing and deafened guinea pig cochleae via a single slow-rate injection. Cochleae were examined between 2 h and 28 days post-infusion by autoradiography or fluorescent microscopy to determine the number of turns labeled by NT-3, identify individual cells and tissues receiving NT-3 and quantify the proportion of signal in each tissue. In general, long-term infusions were required for all cochlear turns to receive NT-3. (125)I NT-3 signal was strongest in cells lining the perilymphatic space of the scala tympani, basilar membrane, osseous spiral lamina and spiral ligament. Signal in the peripheral nerve tract and Rosenthal's canal was only 1.3-2.1 times background levels of radiation. NT-3 microspheres were detected within neural areas of the cochlea (nerve tract and Rosenthal's canal) in all cases, but not within neuronal cell bodies. NT-3 microspheres remained in the cochlea for at least 28 days, suggesting a low clearance rate within cochlear tissues.

Analysis of Variance↗

PubMed2005

Sustained cadherin 23 expression in young and adult cochlea of normal and hearing-impaired mice.

Cadherin 23 encodes a single-pass transmembrane protein with 27 extracellular cadherin-domains and localizes to stereocilia where it functions as an inter-stereocilia link. Cadherin 23-deficient mice show congenital deafness in combination with circling behavior as a result of organizational defects in the stereocilia hair bundle; common inbred mouse strains carrying the hypomorphic Cdh23(753A) allele are highly susceptible to sensorineural hearing loss. Here, we show that an antibody (N1086) directed against the intracellular carboxyterminus reacts specifically with cadherin 23 and detects with high sensitivity the isoform devoid of the peptide encoded by exon 68 (CDH23Delta68). Cochlea, vestibule, eye, brain and testis produce the CDH23Delta68 isoform in abundance and form moieties with different molecular weight due to variations in glycosylation content. In the cochlea, CDH23Delta68 expression is highest at postnatal day 1 (P1) and P7; expression is down regulated through P14 and P21 and persists at a low steady-state level throughout adulthood (P160). Furthermore, CDH23Delta68 expression levels in young and adult cochlea are similar among normal and hearing deficient strains (C3HeB/FeJ, C57BL/6J and BUB/BnJ). Finally, by immunofluorescence using an antibody (Pb240) specific for ectodomain 14, we show that cadherin 23 localizes to stereocilia during hair bundle development in late gestation and early postnatal days. Cadherin 23-specific labeling becomes weaker as the hair bundle matures but faint labeling concentrated near the top of stereocilia is still detectable at P35. No labeling of cochlea stereocilia was observed with N1086. In conclusion, our data describe a cadherin 23-specific antibody with high affinity to the CDH23Delta68 isoform, reveal a dynamic cochlea expression and localization profile and show sustained cadherin 23 levels in adult cochlea of normal and hearing-impaired mice.

Amino Acid Sequence↗

PubMed2004

Noise exposure induces up-regulation of ecto-nucleoside triphosphate diphosphohydrolases 1 and 2 in rat cochlea.

Extracellular ATP acting via P2 receptors in the inner ear initiates a variety of signaling pathways that may be involved in noise-induced cochlear injury. Nucleoside triphosphate diphosphohydrolase (NTPDase)1/CD39 and NTPDase2/CD39L1 are key elements for regulation of extracellular nucleotide concentrations and P2 receptor signaling in the cochlea. This study characterized the effect of noise exposure on regulation of NTPDase1 and NTPDase2 expression in the cochlea using a combination of real-time RT-PCR, immunohistochemistry and functional studies. Adult Wistar rats were exposed to broad band noise at 90 dB and 110 dB sound pressure level (SPL) for 72 h. Exposure to 90 dB SPL induced a small and temporary change of auditory thresholds (temporary threshold shift), while exposure to 110 dB SPL induced a robust and permanent change of auditory thresholds (permanent threshold shift). NTPDase1 and NTPDase2 mRNA transcripts were upregulated in the cochlea exposed to 110 dB SPL, while mild noise (90 dB SPL) altered only NTPDase1 mRNA expression levels. Changes in NTPDases expression did not correlate with levels of circulating corticosterone, implying that the up-regulation of NTPDases expression was not stress-related. Semi-quantitative immunohistochemistry in the cochlea exposed to 110 dB SPL localized the increased NTPDase1 and NTPDase2 immunostaining in the stria vascularis and up-regulation of NTPDase2 in the intraganglionic spiral bundle. In contrast, NTPDase1 was down-regulated in the cell bodies of the spiral ganglion neurones. Distribution of NTPDases was not altered in the cochlea exposed to 90 dB SPL. Functional studies revealed increased ectonucleotidase activities in the cochlea after exposure to 110 dB SPL, consistent with up-regulation of NTPDases. The changes in NTPDases expression may reflect adaptive response of cochlear tissues to limit ATP signaling during noise exposure.

Acoustic Stimulation↗

PubMed2000

Expression of the GDNF family members and their receptors in the mature rat cochlea.

The GDNF family comprises glial cell line-derived neurotrophic factor (GDNF) and the related proteins neurturin, artemin and persephin, which form a subgroup of the TGF-beta superfamily of growth factors. All four neurotrophic factors provide neuronal cell protection and cell survival. GDNF expression was found in the cochlea, and GDNF has been shown to be effective for inner ear protection from drugs and noise-induced insults. As the other members of the GDNF family also provide protective effects on neuronal cells, they may play important roles in the inner ear. We used RT-PCR to examine the expression of GDNF, neurturin, artemin, persephin and their receptors GFRalpha-1, GFRalpha-2, GFRalpha-3 and c-ret in whole rat cochlea as well as in functionally different subfractions (modiolus and sensorineural epithelium/lateral wall) and compared the levels of neurotrophin and receptor mRNAs in the cochlea to those in substantia nigra brain region. Our results demonstrate the expression of all GDNF family members and their receptors in cochlea and substantia nigra. However, the relative levels of mRNA were different for several genes tested in subfractions of the cochlea and/or compared to expression levels in substantia nigra. The presence of mRNA for all four members of the GDNF family and their preferred receptors in the rat cochlea suggests potential functional importance of these neurotrophic factors as protection and survival factors in the inner ear.

Animals↗

PubMed2002

Inputs from the cochlea and the inferior colliculus converge on olivocochlear neurones.

Medial olivocochlear (MOC) neurones, located in the superior olivary complex, can suppress cochlear gain by their action on the cochlear outer hair cells. Inputs from the contralateral cochlea and the inferior colliculus (IC) have been separately shown to increase activity of MOC neurones. In this study we have investigated in guinea-pigs under barbiturate anaesthesia the interactions between these two inputs by combining electrical stimulation of the IC with acoustic stimulation of the contralateral cochlea. Electrical stimulation of the IC resulted in a significant suppression of the amplitude of the compound action potential (CAP) of the auditory nerve to test tones. This suppression was equivalent to an average decrease in sound intensity of 5.7 dB and 3.7 dB for contralateral and ipsilateral stimulation, respectively. Acoustic stimulation of the contralateral cochlea with broadband noise produced no detectable change in the amplitude of the CAP in the test cochlea in all but one animal. However, simultaneous electrical stimulation of the IC and acoustic stimulation of the contralateral cochlea resulted in a reduction in CAP amplitude that was markedly larger than that produced by IC stimulation alone. The suppression with the addition of contralateral noise was equivalent to a mean reduction in sound intensity of 8.7 dB with contralateral and 5.7 dB with ipsilateral IC stimulation. We hypothesise that excitatory input from the contralateral cochlea converges with excitatory input from the IC on the MOC neurones and in this way augments the activity of these neurones, resulting in a larger peripheral effect.

Acoustic Stimulation↗

PubMed2002

Aquaporin-2 expression in the mammalian cochlea and investigation of its role in Meniere's disease.

The expression pattern of aquaporin-2 (AQP2), a vasopressin regulated member of the aquaporin gene family, in the cochlea and its potential role in Meniere's disease was investigated. RT-PCR screen of multiple rat tissues identified AQP2 transcripts in the cochlea, testis and kidney and an absence of tissue-specific splice variants. The level of AQP2 transcript in the cochlea was 10-fold lower relative to its expression in the testis and kidney. Western blot analysis demonstrated a single, 29 kDa band in the membrane fractions from cochlea, testis and the kidney. In the rat and mouse cochlea, AQP2 was expressed in the structures bordering the endolymph, including Reissner's membrane, the organ of Corti, inner and outer sulcus cells and the spiral limbus. A mutation screen of AQP2 in 12 individuals with Meniere's disease did not identify any sequence alterations or mutations within the four coding exons of AQP2 and their intron-exon junctions. The physiological role of AQP2 in water transport and its expression pattern in the cochlea suggests an important role for AQP2 in fluid homeostasis of the inner ear; however, its role in the pathogenesis in Meniere's disease remains to be established.

Animals↗

PubMed2002

Dystroglycan expression in the developing and senescent gerbil cochlea.

Dystroglycan (DG) forms part of a cell surface laminin receptor complex and is believed to play a critical role in the assembly and homeostasis of basement membranes (BM). The receptor complex is made up of alpha- and beta-DG subunits and is found in muscle, epithelial and nerve tissue. In the cochlea, DG may be involved in the abnormal accumulation of laminin seen in the thickened BM of strial capillaries with age. This excess deposition of laminin is thought to lead to capillary necrosis and contribute to degeneration of the stria vascularis (SV). Here we assessed the presence and distribution of DG in the developing, mature and senescent gerbil cochlea in order to ascertain whether altered patterns of expression are a factor in age-related pathology. Western blots of proteins isolated from the entire cochlea demonstrated the presence of the alpha-DG subunit. mRNA encoding DG was identified in microdissected specimens of the lateral wall and the combined organ of Corti/modiolus by RT-PCR analysis. Immunohistochemical experiments localized alpha-DG in epithelial BMs and regions of epithelial cell-cell contact with no intervening BM in the developing and mature cochlea. Immunoreactive alpha-DG was present in the BM underlying strial capillaries and in vessels of the central portion of the auditory nerve, but was not detected in any other vessels in the cochlea. Age-related changes in alpha-DG expression were observed only in the SV where a marked decrease in alpha-DG immunoreactivity was seen in the BM of strial capillaries as well as throughout the SV. The results demonstrate the selective expression of alpha-DG in both BM and non-BM sites in the mature cochlea and suggests its involvement in both developmental and aging processes.

Aging↗