Organ of Corti explants direct tonotopically graded morphology of spiral ganglion neurons in vitro

The spiral ganglion neurons (SGNs) are the primary afferent neurons in the spiral ganglion (SG), while their degeneration or loss would cause sensorineural hearing loss. As a cardiac-derived hormone, atrial natriuretic peptide (ANP) plays a critical role in cardiovascular homeostasis through binding to its functional receptors (NPR-A and NPR-C). ANP and its receptors are widely expressed in the mammalian nervous system where they could be implicated in the regulation of multiple neural functions. Although previous studies have provided direct evidence for the presence of ANP and its functional receptors in the inner ear, their presence within the cochlear SG and their regulatory roles during auditory neurotransmission and development remain largely unknown. Based on our previous findings, we investigated the expression patterns of ANP and its receptors in the cochlear SG and dissociated SGNs and determined the influence of ANP on neurite outgrowth in vitro by using organotypic SG explants and dissociated SGN cultures from postnatal rats. We have demonstrated that ANP and its receptors are expressed in neurons within the cochlear SG of postnatal rat, while ANP may promote neurite outgrowth of SGNs via the NPR-A/cGMP/PKG pathway in a dose-dependent manner. These results indicate that ANP would play a role in normal neuritogenesis of SGN during cochlear development and represents a potential therapeutic candidate to enhance regeneration and regrowth of SGN neurites.

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Functional Role of Neurotrophin-3 in Synapse Regeneration by Spiral Ganglion Neurons on Inner Hair Cells after Excitotoxic Trauma In Vitro

Journal of Neuroscience ◽

10.1523/jneurosci.1434-10.2011 ◽

2011 ◽

Vol 31 (21) ◽

pp. 7938-7949 ◽

Cited By ~ 89

Author(s):

Q. Wang ◽

S. H. Green

Keyword(s):

Hair Cells ◽

Functional Role ◽

Spiral Ganglion ◽

Spiral Ganglion Neurons ◽

Inner Hair Cells ◽

Neurotrophin 3 ◽

Ganglion Neurons

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Simvastatin Results in a Dose-Dependent Toxic Effect on Spiral Ganglion Neurons in anIn VitroOrganotypic Culture Assay

BioMed Research International ◽

10.1155/2016/3580359 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Katharina Leitmeyer ◽

Andrea Glutz ◽

Cristian Setz ◽

Leonie Wieland ◽

Sulamith Egloff ◽

...

Keyword(s):

Mevalonate Pathway ◽

Neuronal Survival ◽

Spiral Ganglion ◽

Spiral Ganglion Neurons ◽

Supporting Cells ◽

Simvastatin Treatment ◽

Dose Dependent Decrease ◽

Ganglion Neurons ◽

Dose Dependent

Statins are inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an enzyme necessary for the production of mevalonate. They are widely used as cholesterol-lowering drugs. However, conflicting data about the effect of statins on neuronal cells has been published. To explore the effect of simvastatin on spiral ganglion neurons (SGNs), SG explants of 5-day-old rats were treated with increasing concentrations of simvastatin. In addition, SG explants were treated with mevalonate and with the combination of simvastatin and mevalonate. SGN number, length of the neurites, area of nonneuronal supporting cells, and neuronal survival were analyzed. Simvastatin treatment results in a significant dose-dependent decrease of SG neurite number, length of neurites, area of supporting cells, and SG neuronal survival compared to control. Interestingly, treatment with mevalonate in addition to simvastatin increased SG neuronal survival compared to simvastatin treatment only. However, treatment with mevalonate in addition to simvastatin did not influence SG neurite number, length of neurites, and area of supporting cells compared to simvastatin treatment only. Our results suggest a neurotoxic effect of simvastatin on SGNsin vitro. Neurotoxicity seems to be at least partially mediated by the mevalonate pathway. Therefore, caution is warranted to use simvastatin as a potential otoprotective drug.

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Correction to: Influence of In Vitro Electrical Stimulation on Survival of Spiral Ganglion Neurons

Neurotoxicity Research ◽

10.1007/s12640-019-00029-7 ◽

2019 ◽

Vol 36 (1) ◽

pp. 217-217

Author(s):

Marvin N. Peter ◽

Athanasia Warnecke ◽

Uta Reich ◽

Heidi Olze ◽

Agnieszka J. Szczepek ◽

...

Keyword(s):

Electrical Stimulation ◽

Spiral Ganglion ◽

Spiral Ganglion Neurons ◽

Ganglion Neurons

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Atrial Natriuretic Peptide Promotes Neurite Outgrowth and Survival of Cochlear Spiral Ganglion Neurons in vitro Through NPR-A/cGMP/PKG Signaling

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.681421 ◽

2021 ◽

Vol 9 ◽

Author(s):

Fei Sun ◽

Ke Zhou ◽

Ke-yong Tian ◽

Xin-yu Zhang ◽

Wei Liu ◽

...

Keyword(s):

Atrial Natriuretic Peptide ◽

Neurite Outgrowth ◽

Natriuretic Peptide ◽

Neuronal Survival ◽

Spiral Ganglion ◽

Bioactive Molecules ◽

Spiral Ganglion Neurons ◽

Ganglion Neurons ◽

Atrial Natriuretic

Sensorineural hearing loss (SNHL) is a dominant public health issue affecting millions of people around the globe, which is correlated with the irreversible deterioration of the hair cells and spiral ganglion neurons (SGNs) within the cochlea. Strategies using bioactive molecules that regulate neurite regeneration and neuronal survival to reestablish connections between auditory epithelium or implanted electrodes and SGN neurites would become attractive therapeutic candidates for SNHL. As an intracellular second messenger, cyclic guanosine-3’,5’-monophosphate (cGMP) can be synthesized through activation of particulate guanylate cyclase-coupled natriuretic peptide receptor by natriuretic peptides, which in turn modulates multiple aspects of neuronal functions including neuronal development and neuronal survival. As a cardiac-derived hormone, atrial natriuretic peptide (ANP), and its specific receptors (NPR-A and NPR-C) are broadly expressed in the nervous system where they might be involved in the maintenance of diverse neural functions. Despite former literatures and our reports indicating the existence of ANP and its receptors within the inner ear, particularly in the spiral ganglion, their potential regulatory mechanisms underlying functional properties of auditory neurons are still incompletely understood. Our recently published investigation revealed that ANP could promote the neurite outgrowth of SGNs by activating NPR-A/cGMP/PKG cascade in a dose-dependent manner. In the present research, the influence of ANP and its receptor-mediated downstream signaling pathways on neurite outgrowth, neurite attraction, and neuronal survival of SGNs in vitro was evaluated by employing cultures of organotypic explant and dissociated neuron from postnatal rats. Our data indicated that ANP could support and attract neurite outgrowth of SGNs and possess a high capacity to improve neuronal survival of SGNs against glutamate-induced excitotoxicity by triggering the NPR-A/cGMP/PKG pathway. The neuroregenerative and neuroprotective effects of ANP/NPRA/cGMP/PKG-dependent signaling on SGNs would represent an attractive therapeutic candidate for hearing impairment.

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

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.751012 ◽

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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