Changes in Guinea Pig Cochlear Hair Cells after Sound Conditioning and Noise Exposure

AbstractCurrent clinical interest lies in the relationship between hearing loss and cognitive impairment. Previous work demonstrated that noise exposure, a common cause of sensorineural hearing loss (SNHL), leads to cognitive impairments in mice. However, in noise-induced models, it is difficult to distinguish the effects of noise trauma from subsequent SNHL on central processes. Here, we use cochlear hair cell ablation to isolate the effects of SNHL. Cochlear hair cells were conditionally and selectively ablated in mature, transgenic mice where the human diphtheria toxin (DT) receptor was expressed behind the hair-cell specific Pou4f3 promoter. Due to higher Pou4f3 expression in cochlear hair cells than vestibular hair cells, administration of a low dose of DT caused profound SNHL without vestibular dysfunction and had no effect on wild-type (WT) littermates. Spatial learning/memory was assayed using an automated radial 8-arm maze (RAM), where mice were trained to find food rewards over a 14-day period. The number of working memory errors (WME) and reference memory errors (RME) per training day were recorded. All animals were injected with DT during P30–60 and underwent the RAM assay during P90–120. SNHL animals committed more WME and RME than WT animals, demonstrating that isolated SNHL affected cognitive function. Duration of SNHL (60 versus 90 days post DT injection) had no effect on RAM performance. However, younger age of acquired SNHL (DT on P30 versus P60) was associated with fewer WME. This describes the previously undocumented effect of isolated SNHL on cognitive processes that do not directly rely on auditory sensory input.

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Apoptosis of guinea pig cochlear hair cells following chronic aminoglycoside treatment

European Archives of Oto-Rhino-Laryngology ◽

10.1007/s004050050027 ◽

1998 ◽

Vol 255 (3) ◽

pp. 127-131 ◽

Cited By ~ 50

Author(s):

T. Nakagawa ◽

H. Yamane ◽

M. Takayama ◽

K. Sunami ◽

Y. Nakai

Keyword(s):

Guinea Pig ◽

Hair Cells ◽

Cochlear Hair Cells

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Single Ototopical Application of Mesna Has No Ototoxic Effects on Guinea Pig Cochlear Hair Cells: A Morphological Study

Acta Oto-Laryngologica ◽

10.1080/00016489950180630 ◽

1999 ◽

Vol 119 (6) ◽

pp. 685-689 ◽

Cited By ~ 7

Author(s):

M. P. van Spaendonck

Keyword(s):

Guinea Pig ◽

Hair Cells ◽

Morphological Study ◽

Cochlear Hair Cells

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The integrity of cochlear hair cells is established and maintained through the localization of Dia1 at apical junctional complexes and stereocilia

Cell Death and Disease ◽

10.1038/s41419-020-02743-z ◽

2020 ◽

Vol 11 (7) ◽

Author(s):

Yuzuru Ninoyu ◽

Hirofumi Sakaguchi ◽

Chen Lin ◽

Toshiaki Suzuki ◽

Shigeru Hirano ◽

...

Keyword(s):

Hearing Loss ◽

Hair Cells ◽

Noise Exposure ◽

Spiral Ganglion ◽

Cell Junctions ◽

Ultrastructural Changes ◽

Apical Surface ◽

Progressive Hearing Loss ◽

Cochlear Hair Cells ◽

Junctional Complexes

AbstractDia1, which belongs to the diaphanous-related formin family, influences a variety of cellular processes through straight actin elongation activity. Recently, novel DIA1 mutants such as p.R1213X (p.R1204X) and p.A265S, have been reported to cause an autosomal dominant sensorineural hearing loss (DFNA1). Additionally, active DIA1 mutants induce progressive hearing loss in a gain-of-function manner. However, the subcellular localization and pathological function of DIA1(R1213X/R1204X) remains unknown. In the present study, we demonstrated the localization of endogenous Dia1 and the constitutively active DIA1 mutant in the cochlea, using transgenic mice expressing FLAG-tagged DIA1(R1204X) (DIA1-TG). Endogenous Dia1 and the DIA1 mutant were regionally expressed at the organ of Corti and the spiral ganglion from early life; alongside cochlear maturation, they became localized at the apical junctional complexes (AJCs) between hair cells (HCs) and supporting cells (SCs). To investigate HC vulnerability in the DIA1-TG mice, we exposed 4-week-old mice to moderate noise, which induced temporary threshold shifts with cochlear synaptopathy and ultrastructural changes in stereocilia 4 weeks post noise exposure. Furthermore, we established a knock-in (KI) mouse line expressing AcGFP-tagged DIA1(R1213X) (DIA1-KI) and confirmed mutant localization at AJCs and the tips of stereocilia in HCs. In MDCKAcGFP-DIA1(R1213X) cells with stable expression of AcGFP-DIA1(R1213X), AcGFP-DIA1(R1213X) revealed marked localization at microvilli on the apical surface of cells and decreased localization at cell-cell junctions. The DIA1-TG mice demonstrated hazy and ruffled circumferential actin belts at AJCs and abnormal stereocilia accompanied with HC loss at 5 months of age. In conclusion, Dia1 plays a pivotal role in the development and maintenance of AJCs and stereocilia, ensuring cochlear and HC integrity. Subclinical/latent vulnerability of HCs may be the cause of progressive hearing loss in DFNA1 patients, thus suggesting new therapeutic targets for preventing HC degeneration and progressive hearing loss associated with DFNA1.

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