Age-related changes in the murine cochlear lateral wall

Ichimiya, Issei; Suzuki, Masashi; Mogi, Goro

doi:10.1016/s0378-5955(99)00170-7

Cited by 61 publications

(42 citation statements)

References 19 publications

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“…Occasional thinning of the fibrocytes in the spiral limbus was also seen at the apex of some cochleae. These changes could be a related to aging in the 6.5-month-old ears because they have a C57BL/6J background (Francis et al 2003;Ichimiya et al 2000). All control ears had normalappearing vestibular neuroepithelia (Fig.…”

Section: Light Microscopic Findings In Adult Micementioning

confidence: 96%

Progression of Inner Ear Pathology in Ames Waltzer Mice and the Role of Protocadherin 15 in Hair Cell Development

Pawlowski

Kikkawa²,

Wright

et al. 2006

JARO

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The Ames waltzer (av) mouse mutant exhibits auditory and vestibular abnormalities resulting from mutation of protocadherin 15 (Pcdh15). Ames waltzer has been identified as an animal model for inner ear pathology associated with Usher syndrome type 1F. Studies correlating anatomical phenotype with severity of genetic defect in various av alleles are providing better understanding of the role played by Pcdh15 in inner ear development and of sensorineural abnormalities associated with alterations in Pcdh15 protein structure as a result of gene mutation. In this work we present new findings on inner ear pathology in four alleles of av mice with differing mutations of Pcdh15 as well as varying alterations in inner ear morphology. Two alleles with in-frame deletion mutations (Pcdh15 av-J and Pcdh15 av-2J ) and two presumptive functional null alleles (Pcdh15 av-3J and Pcdh15 av-Tg ) were studied. Light and electron microscopic observations demonstrated that the severity of cochlear and vestibular pathology in these animals correlates positively with the extent of mutation in Pcdh15 from embryonic day 18 (E18) up to 12 months. Electron microscopic analysis of immature ears indicated early abnormalities in the arrangement of stereocilia and the inner and outer hair cell cuticular plates, stereocilia rootlets, and the actin meshwork within the cuticular plate. In severe cases, displacement of the kinocilium and alterations in the shape of the cuticular plate was also observed. Mice harboring inframe deletion mutations showed less disorganization of stereocilia and cuticular plates in the organ of Corti than the presumptive functional null alleles at P0-P10. A slower progression of pathology was also seen via light microscopy in older animals with inframe deletions, compared to the presumptive functional null mutations. In summary, our results demonstrate that mutation in Pcdh15 affects the initial formation of stereocilia bundles with associated changes in the actin meshwork within the cuticular plate; these effects are more pronounced in the presumed null mutation compared to mutations that only affect the extracellular domain. The positive correlation of severity of effects with extent of mutation can be seen well into adulthood.

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Section: Light Microscopic Findings In Adult Micementioning

confidence: 96%

Progression of Inner Ear Pathology in Ames Waltzer Mice and the Role of Protocadherin 15 in Hair Cell Development

Pawlowski

Kikkawa²,

Wright

et al. 2006

JARO

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“…Information thus remains limited about the``core'' attributes of Ahl (i.e., those traits least subject to genetic modi®cation). Ahl has been implicated in degeneration of the stria vascularis and spiral ligament in C57BL/6 and related strains (Mikaelian 1979;Ichimiya et al 2000;Hequembourg and Liberman 2001). Where these have been observed, they appear modest and may not contribute to hearing loss (Schuknecht 1974; Schulte and Schmiedt 1992).…”

Section: Mouse Ahl As a Model For Human Arhlmentioning

confidence: 99%

“…Cochlear degeneration in these models begins early in adulthood and includes hair cell loss and primary neuronal loss (Henry 1983;Saitoh et al 1995;Spongr et al 1997;Willott et al 1998). Degeneration of stria vascularis and spiral ligament may eventually follow (Saitoh et al 1995;Ichimiya et al 2000;Hequembourg and Liberman 2001).…”

Section: Introductionmentioning

confidence: 99%

“…Although studies indicate that both C57BL/6 and BALB/c mice show hair cell loss and primary neuronal loss (Spongr et al 1997;Willott et al 1998;Hequembourg and Liberman 2001), whether they share pathology of stria and spiral ligament is not well established. Willott et al (1998) reported that stria vascularis appears normal in aging BALB/c mice, while abnormalities of the stria/spiral ligament in C57BL/6 and closely related strains have been repeatedly described (Mikaelian 1979;Ichimiya et al 2000;Hequembourg and Liberman 2001). We evaluated cochleas of BALB/cJ mice that varied in age (1.5±13.0 mos) and noise history.…”

Section: Introductionmentioning

confidence: 99%

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Reduction in Sharpness of Frequency Tuning but not Endocochlear Potential in Aging and Noise-Exposed BALB/cJ Mice

Ohlemiller

2002

JARO - Journal of the Association for Research in Otolaryngolog

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Schuknecht proposed categories for human age-related hearing loss (ARHL) based upon whether the primary degeneration involves the organ of Corti (sensory ARHL), spiral ganglion cells (neural), stria vascularis (strial), or a combination of these (mixed). Genetically standardized mouse ARHL models can help validate Schuknecht's framework and clarify the underlying cellular processes. Much recent work has focused on the mouse Ahl locus, which promotes both ARHL and noise-induced hearing loss. On the C57BL/6 inbred background, Ahl has been associated with degeneration of organ of Corti, afferent neurons, and stria vascularis/spiral ligament, suggesting that it promotes mixed (sensory/neural/strial) ARHL. Some cochlear degeneration in C57BL/6 mice could be caused by genes other than Ahl, however. The question of what constitutes Ahl-related pathology can be addressed by comparing C57BL/6 mice with other strains that carry the same allele, including BALB/c substrains. We examined the effects of aging and broadband noise exposure in inbred BALB/cJ mice (1.5±13.0 mos) using measures of frequency tuning (compound action potential tuning curves) (CAPTCs), strial function (endocochlear potential recording, EP), and light microscopy. Aging and noise led to generally similar physiological and anatomical changes. Reductions in sensitivity and sharpness of frequency tuning were not consistently linked to hair cell loss, reduction in the EP, or changes in the lateral wall. Instead they appeared best explained by alterations in supporting cells in the basal half of the cochlear and in the spiral limbus in the apex. These results emphasize the importance of cell types other than hair cells in cochlear pathology. They also indicate that Ahl does not necessarily promote a strial form of ARHL.

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“…AHL has been attributed to pathological and functional degeneration in the cochlear lateral wall, including atrophy of stria vascularis, reduced staining of Na + ,K + -ATPase and connexin 26, and the decline of EP in aged gerbils (Gratton et al 1996;Ichimiya et al 2000;Schmiedt 1996). Spiral ligament degeneration was observed as a loss of fibrocytes in aged C57BL/6 mice (Hequembourg and Liberman 2001).…”

Section: Introductionmentioning

confidence: 99%

Age-Related Changes in Cochlear Endolymphatic Potassium and Potential in CD-1 and CBA/CaJ Mice

Marcus

2003

JARO - Journal of the Association for Research in Otolaryngolog

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The CD-1 mouse strain is known to have early onset of hearing loss that is progressive with aging. We sought to determine whether a disturbance of K + homeostasis and pathological changes in the cochlear lateral wall were involved in the age-related hearing loss (AHL) of CD-1 as compared to the CBA/CaJ strain which has minimal AHL. In the present study, the endocochlear potential (EP) and endolymphatic K + concentration ([K + ] e ) were measured in both strains of mice with double-barrel microelectrodes at ''young'' (1-2 mo) and ''old'' (5-9 mo) ages. CBA/ CaJ mice displayed no changes with aging in EP and [K + ] e of the basal turn. In the apical turn, there was a small positive shift of the EP (10 mV) with aging under both normoxic and acute anoxic conditions ()EP), without any change of [K + ] e . Further, there were no obvious pathological changes in the lateral wall of CBA/CaJ mice. By contrast, old CD-1 mice displayed a significantly reduced [K + ] e by 30% in both basal and apical turns with no significant changes in normoxic EP. The )EP in the apical turn was significantly reduced in magnitude by 6 mV. A severe loss of cells with aging was observed in the region of type IV fibrocytes of the apical and basal turns and of type II fibrocytes in the basal turn. A complete degeneration of organ of Corti was also observed at the basal turn of old CD-1 mice, as well as a basalward decline of spiral ganglion neuron density. The pathological changes in spiral ligament of CD-1 mice were similar to those of an inbred mouse strain C57BL/6J that expresses an AHL gene (ahl) and might be a primary etiology of AHL of CD-1 mice. These findings have ramifications for our understanding of AHL and for interpretation of genetic mutations in a CD-1 background.

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Age-related changes in the murine cochlear lateral wall

Cited by 61 publications

References 19 publications

Progression of Inner Ear Pathology in Ames Waltzer Mice and the Role of Protocadherin 15 in Hair Cell Development

Progression of Inner Ear Pathology in Ames Waltzer Mice and the Role of Protocadherin 15 in Hair Cell Development

Reduction in Sharpness of Frequency Tuning but not Endocochlear Potential in Aging and Noise-Exposed BALB/cJ Mice

Age-Related Changes in Cochlear Endolymphatic Potassium and Potential in CD-1 and CBA/CaJ Mice

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