7,8,3′-Trihydroxyflavone, a potent small molecule TrkB receptor agonist, protects spiral ganglion neurons from degeneration both in vitro and in vivo

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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Cometin is a novel neurotrophic factor that promotes neurite outgrowth and neuroblast migration in vitro and supports survival of spiral ganglion neurons in vivo

Experimental Neurology ◽

10.1016/j.expneurol.2011.09.027 ◽

2012 ◽

Vol 233 (1) ◽

pp. 172-181 ◽

Cited By ~ 22

Author(s):

Jesper Roland Jørgensen ◽

Anette Fransson ◽

Lone Fjord-Larsen ◽

Lachlan H. Thompson ◽

Jeffrey P. Houchins ◽

...

Keyword(s):

Neurite Outgrowth ◽

Neurotrophic Factor ◽

Spiral Ganglion ◽

Spiral Ganglion Neurons ◽

Neuroblast Migration ◽

Ganglion Neurons

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TGF-beta superfamily member activin A acts with BDNF and erythropoietin to improve survival of spiral ganglion neurons in vitro

Neuropharmacology ◽

10.1016/j.neuropharm.2013.08.008 ◽

2013 ◽

Vol 75 ◽

pp. 416-425 ◽

Cited By ~ 23

Author(s):

Odett Kaiser ◽

Gerrit Paasche ◽

Timo Stöver ◽

Stefanie Ernst ◽

Thomas Lenarz ◽

...

Keyword(s):

Spiral Ganglion ◽

Activin A ◽

Spiral Ganglion Neurons ◽

Tgf Beta ◽

Ganglion Neurons

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In Vitro Functional Assessment of Adult Spiral Ganglion Neurons (SGNs)

Methods in Molecular Biology - Auditory and Vestibular Research ◽

10.1007/978-1-4939-3615-1_29 ◽

2016 ◽

pp. 513-523 ◽

Cited By ~ 5

Author(s):

Jeong Han Lee ◽

Choongryoul Sihn ◽

Wanging Wang ◽

Cristina Maria Perez Flores ◽

Ebenezer N. Yamoah

Keyword(s):

Functional Assessment ◽

Spiral Ganglion ◽

Spiral Ganglion Neurons ◽

Ganglion Neurons

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Atrial Natriuretic Peptide Improves Neurite Outgrowth from Spiral Ganglion Neurons In Vitro through a cGMP-Dependent Manner

Neural Plasticity ◽

10.1155/2020/8831735 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Fei Sun ◽

Ke Zhou ◽

Ke-yong Tian ◽

Jie Wang ◽

Jian-hua Qiu ◽

...

Keyword(s):

Atrial Natriuretic Peptide ◽

Neurite Outgrowth ◽

Natriuretic Peptide ◽

Critical Role ◽

Spiral Ganglion ◽

Spiral Ganglion Neurons ◽

Dependent Manner ◽

Ganglion Neurons ◽

Atrial Natriuretic

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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