Prosurvival and proapoptotic intracellular signaling in rat spiral ganglion neurons in vivo after the loss of hair cells

2007 ◽  
Vol 503 (6) ◽  
pp. 832-852 ◽  
Author(s):  
Shaheen A. Alam ◽  
Barbara K. Robinson ◽  
Jie Huang ◽  
Steven H. Green
Keyword(s):  
Hair Cells ◽  
Intracellular Signaling ◽  
Spiral Ganglion ◽  
Spiral Ganglion Neurons ◽  
Ganglion Neurons

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.

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 Exocyst Complex Member EXOC5 Is Required for Survival of Hair Cells and Spiral Ganglion Neurons and Maintenance of Hearing

2018 ◽  
Vol 55 (8) ◽  
pp. 6518-6532 ◽  
Author(s):  
Byeonghyeon Lee ◽  
Jeong-In Baek ◽  
Hyehyun Min ◽  
Seung-Hyun Bae ◽  
Kyeonghye Moon ◽  
...  
Keyword(s):  
Hair Cells ◽  
Spiral Ganglion ◽  
Spiral Ganglion Neurons ◽  
Exocyst Complex ◽  
Ganglion Neurons

scholarly journals Correction to: Exocyst Complex Member EXOC5 Is Required for Survival of Hair Cells and Spiral Ganglion Neurons and Maintenance of Hearing

2019 ◽  
Vol 56 (3) ◽  
pp. 2300-2300
Author(s):  
Byeonghyeon Lee ◽  
Jeong-In Baek ◽  
Hyehyun Min ◽  
Seung-Hyun Bae ◽  
Kyeonghye Moon ◽  
...  
Keyword(s):  
Hair Cells ◽  
Spiral Ganglion ◽  
Spiral Ganglion Neurons ◽  
Exocyst Complex ◽  
Ganglion Neurons

scholarly journals Spatiotemporal Developmental Upregulation of Prestin Correlates With the Severity and Location of Cyclodextrin-Induced Outer Hair Cell Loss and Hearing Loss

2021 ◽  
Vol 9 ◽  
Author(s):  
Dalian Ding ◽  
Haiyan Jiang ◽  
Senthilvelan Manohar ◽  
Xiaopeng Liu ◽  
Li Li ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Auditory Nerve ◽  
High Frequency ◽  
Spiral Ganglion ◽  
Low Frequency ◽  
Nerve Fibers ◽  
Spiral Ganglion Neurons ◽  
Auditory Nerve Fibers ◽  
Ganglion Neurons

2-Hyroxypropyl-beta-cyclodextrin (HPβCD) is being used to treat Niemann-Pick C1, a fatal neurodegenerative disease caused by abnormal cholesterol metabolism. HPβCD slows disease progression, but unfortunately causes severe, rapid onset hearing loss by destroying the outer hair cells (OHC). HPβCD-induced damage is believed to be related to the expression of prestin in OHCs. Because prestin is postnatally upregulated from the cochlear base toward the apex, we hypothesized that HPβCD ototoxicity would spread from the high-frequency base toward the low-frequency apex of the cochlea. Consistent with this hypothesis, cochlear hearing impairments and OHC loss rapidly spread from the high-frequency base toward the low-frequency apex of the cochlea when HPβCD administration shifted from postnatal day 3 (P3) to P28. HPβCD-induced histopathologies were initially confined to the OHCs, but between 4- and 6-weeks post-treatment, there was an unexpected, rapid and massive expansion of the lesion to include most inner hair cells (IHC), pillar cells (PC), peripheral auditory nerve fibers, and spiral ganglion neurons at location where OHCs were missing. The magnitude and spatial extent of HPβCD-induced OHC death was tightly correlated with the postnatal day when HPβCD was administered which coincided with the spatiotemporal upregulation of prestin in OHCs. A second, massive wave of degeneration involving IHCs, PC, auditory nerve fibers and spiral ganglion neurons abruptly emerged 4–6 weeks post-HPβCD treatment. This secondary wave of degeneration combined with the initial OHC loss results in a profound, irreversible hearing loss.

scholarly journals Caffeine Induces Autophagy and Apoptosis in Auditory Hair Cells via the SGK1/HIF-1α Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaomin Tang ◽  
Yuxuan Sun ◽  
Chenyu Xu ◽  
Xiaotao Guo ◽  
Jiaqiang Sun ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Stria Vascularis ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Spiral Ganglion Neurons ◽  
Auditory Hair Cells ◽  
Qrt Pcr ◽  
Ganglion Neurons

Caffeine is being increasingly used in daily life, such as in drinks, cosmetics, and medicine. Caffeine is known as a mild stimulant of the central nervous system, which is also closely related to neurologic disease. However, it is unknown whether caffeine causes hearing loss, and there is great interest in determining the effect of caffeine in cochlear hair cells. First, we explored the difference in auditory brainstem response (ABR), organ of Corti, stria vascularis, and spiral ganglion neurons between the control and caffeine-treated groups of C57BL/6 mice. RNA sequencing was conducted to profile mRNA expression differences in the cochlea of control and caffeine-treated mice. A CCK-8 assay was used to evaluate the approximate concentration of caffeine. Flow cytometry, TUNEL assay, immunocytochemistry, qRT-PCR, and Western blotting were performed to detect the effects of SGK1 in HEI-OC1 cells and basilar membranes. In vivo research showed that 120 mg/ kg caffeine injection caused hearing loss by damaging the organ of Corti, stria vascularis, and spiral ganglion neurons. RNA-seq results suggested that SGK1 might play a vital role in ototoxicity. To confirm our observations in vitro, we used the HEI-OC1 cell line, a cochlear hair cell-like cell line, to investigate the role of caffeine in hearing loss. The results of flow cytometry, TUNEL assay, immunocytochemistry, qRT-PCR, and Western blotting showed that caffeine caused autophagy and apoptosis via SGK1 pathway. We verified the interaction between SGK1 and HIF-1α by co-IP. To confirm the role of SGK1 and HIF-1α, GSK650394 was used as an inhibitor of SGK1 and CoCl2 was used as an inducer of HIF-1α. Western blot analysis suggested that GSK650394 and CoCl2 relieved the caffeine-induced apoptosis and autophagy. Together, these results indicated that caffeine induces autophagy and apoptosis in auditory hair cells via the SGK1/HIF-1α pathway, suggesting that caffeine may cause hearing loss. Additionally, our findings provided new insights into ototoxic drugs, demonstrating that SGK1 and its downstream pathways may be potential therapeutic targets for hearing research at the molecular level.

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