scholarly journals EphA7 regulates spiral ganglion innervation of cochlear hair cells

2015 ◽  
Vol 76 (4) ◽  
pp. 452-469 ◽  
Author(s):  
Young J. Kim ◽  
Leena A. Ibrahim ◽  
Sheng-Zhi Wang ◽  
Wei Yuan ◽  
Oleg V. Evgrafov ◽  
...  
Keyword(s):  
Hair Cells ◽  
Spiral Ganglion ◽  
Cochlear Hair Cells

New insights into glutamate ototoxicity in cochlear hair cells and spiral ganglion neurons

2010 ◽  
Vol 130 (12) ◽  
pp. 1316-1323 ◽  
Author(s):  
Haitao Lu ◽  
Xiang Wang ◽  
Wenyan Sun ◽  
Yao Hu ◽  
Shusheng Gong
Keyword(s):  
Hair Cells ◽  
Spiral Ganglion ◽  
Spiral Ganglion Neurons ◽  
Cochlear Hair Cells ◽  
Ganglion Neurons

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

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.

scholarly journals Anti-inflammatory compounds improve spiral ganglion neuron survival after aminoglycoside-induced hair cell loss in rats

2021 ◽  
Author(s):  
Muhammad T. Rahman ◽  
Erin M. Bailey ◽  
Benjamin M. Gansemer ◽  
Andrew Pieper ◽  
J. Robert Manak ◽  
...  
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Spiral Ganglion ◽  
Cell Loss ◽  
Spiral Ganglion Neuron ◽  
Auditory Information ◽  
Activated Macrophages ◽  
Hair Cell Loss ◽  
Cochlear Hair Cells ◽  
Ganglion Neurons

AbstractSpiral ganglion neurons (SGNs) relay auditory information from cochlear hair cells to the central nervous system. After hair cells are destroyed by aminoglycoside antibiotics, SGNs gradually die. However, the reasons for this cochlear neurodegeneration are unclear. We used microarray gene expression profiling to assess transcriptomic changes in the spiral ganglia of kanamycin-deafened and age-matched control rats and found that many of the genes upregulated after deafening are associated with immune/inflammatory responses. In support of this, we observed increased numbers of macrophages in the spiral ganglion of deafened rats. We also found, via CD68 immunoreactivity, an increase in activated macrophages after deafening. An increase in CD68-associated nuclei was observed by postnatal day 23, a time before significant SGN degeneration is observed. Finally, we show that the immunosuppressive drugs dexamethasone and ibuprofen, as well as the NAD salvage pathway activator P7C3, provide at least some neuroprotection post-deafening. Ibuprofen and dexamethasone also decreased the degree of macrophage activation. These results suggest that activated macrophages specifically, and perhaps a more general neuroinflammatory response, are actively contributing to SGN degeneration after hair cell loss.

scholarly journals Age-Related Hearing Loss and Degeneration of Cochlear Hair Cells in Mice Lacking Thyroid Hormone Receptor β1

Endocrinology ◽  
2015 ◽  
Vol 156 (10) ◽  
pp. 3853-3865 ◽  
Author(s):  
Lily Ng ◽  
Emily Cordas ◽  
Xuefeng Wu ◽  
Kristen R. Vella ◽  
Anthony N. Hollenberg ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Thyroid Hormone ◽  
Hair Cells ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Spiral Ganglion ◽  
Spiral Ligament ◽  
Root Cells ◽  
Cochlear Hair Cells ◽  
Age Related

A key function of the thyroid hormone receptor β (Thrb) gene is in the development of auditory function. However, the roles of the 2 receptor isoforms, TRβ1 and TRβ2, expressed by the Thrb gene are unclear, and it is unknown whether these isoforms promote the maintenance as well as development of hearing. We investigated the function of TRβ1 in mice with a Thrbb1 reporter allele that expresses β-galactosidase instead of TRβ1. In the immature cochlea, β-galactosidase was detected in the greater epithelial ridge, sensory hair cells, spiral ligament, and spiral ganglion and in adulthood, at low levels in the hair cells, support cells and root cells of the outer sulcus. Although deletion of all TRβ isoforms causes severe, early-onset deafness, deletion of TRβ1 or TRβ2 individually caused no obvious hearing loss in juvenile mice. However, over subsequent months, TRβ1 deficiency resulted in progressive loss of hearing and loss of hair cells. TRβ1-deficient mice had minimal changes in serum thyroid hormone and thyrotropin levels, indicating that hormonal imbalances were unlikely to cause hearing loss. The results suggest mutually shared roles for TRβ1 and TRβ2 in cochlear development and an unexpected requirement for TRβ1 in the maintenance of hearing in adulthood.

Cochlear Pathology of Sensorineural Deafness in Cats: Coadministration of Kanamycin and Aminooxyacetic Acid

1987 ◽  
Vol 96 (1_suppl) ◽  
pp. 48-50 ◽  
Author(s):  
P. A. Leake ◽  
R. L. Snyder ◽  
C. E. Schreiner
Keyword(s):  
Body Weight ◽  
Hair Cells ◽  
Time Course ◽  
Spiral Ganglion ◽  
Sensorineural Deafness ◽  
Aminooxyacetic Acid ◽  
Spiral Ganglion Neurons ◽  
Cochlear Hair Cells ◽  
Total Destruction ◽  
Ganglion Neurons

The coadministration of kanamycin (400 mg/kg body weight, s.c.) and aminooxyacetic acid (25 mg/kg body weight, s.c.) results in rapid, total destruction of cochlear hair cells in cats. This drug combination is safer and the time course of hearing losses is less variable than with administration of aminoglycosides alone. Uniform survival of spiral ganglion neurons at 2 and 4 weeks after drug administration suggests a time course similar to that previously observed in neomycin-deafened cats, but more data with longer survival periods are needed to verify these preliminary observations.

scholarly journals Ouabain-Induced Apoptosis in Cochlear Hair Cells and Spiral Ganglion NeuronsIn Vitro

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Yong Fu ◽  
Dalian Ding ◽  
Lei Wei ◽  
Haiyan Jiang ◽  
Richard Salvi
Keyword(s):  
Hair Cells ◽  
Gene Array ◽  
Spiral Ganglion ◽  
Spiral Ganglion Neuron ◽  
Round Window Membrane ◽  
Spiral Ganglion Neurons ◽  
Cochlear Hair Cells ◽  
Ganglion Neurons

Ouabain is a common tool to explore the pathophysiological changes in adult mammalian cochleain vivo. In prior studies, locally administering ouabain via round window membrane demonstrated that the ototoxic effects of ouabainin vivovaried among mammalian species. Little is known about the ototoxic effectsin vitro. Thus, we prepared cochlear organotypic cultures from postnatal day-3 rats and treated these cultures with ouabain at 50, 500, and 1000 μM for different time to elucidate the ototoxic effects of ouabainin vitroand to provide insights that could explain the comparative ototoxic effects of ouabainin vivo. Degeneration of cochlear hair cells and spiral ganglion neurons was evaluated by hair-cell staining and neurofilament labeling, respectively. Annexin V staining was used to detect apoptotic cells. A quantitative RT-PCR apoptosis-focused gene array determined changes in apoptosis-related genes. The results showed that ouabain-induced damagein vitrowas dose and time dependent. 500 μM ouabain and 1000 μM ouabain were destructively traumatic to both spiral ganglion neurons and cochlear hair cells in an apoptotic signal-dependent pathway. The major apoptotic pathways in ouabain-induced spiral ganglion neuron apoptosis culminated in the stimulation of the p53 pathway and triggering of apoptosis by a network of proapoptotic signaling pathways.

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