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

2013 ◽  
Vol 75 ◽  
pp. 416-425 ◽  
Author(s):  
Odett Kaiser ◽  
Gerrit Paasche ◽  
Timo Stöver ◽  
Stefanie Ernst ◽  
Thomas Lenarz ◽  
...  
Author(s):  
Jeong Han Lee ◽  
Choongryoul Sihn ◽  
Wanging Wang ◽  
Cristina Maria Perez Flores ◽  
Ebenezer N. Yamoah

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Fei Sun ◽  
Ke Zhou ◽  
Ke-yong Tian ◽  
Jie Wang ◽  
Jian-hua Qiu ◽  
...  

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.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Katharina Leitmeyer ◽  
Andrea Glutz ◽  
Cristian Setz ◽  
Leonie Wieland ◽  
Sulamith Egloff ◽  
...  

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.


2019 ◽  
Vol 36 (1) ◽  
pp. 217-217
Author(s):  
Marvin N. Peter ◽  
Athanasia Warnecke ◽  
Uta Reich ◽  
Heidi Olze ◽  
Agnieszka J. Szczepek ◽  
...  

Author(s):  
Fei Sun ◽  
Ke Zhou ◽  
Ke-yong Tian ◽  
Xin-yu Zhang ◽  
Wei Liu ◽  
...  

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.


2002 ◽  
Vol 112 (11) ◽  
pp. 2057-2061 ◽  
Author(s):  
Daniel Bodmer ◽  
Bertrand Gloddek ◽  
Allen F. Ryan ◽  
Jochen Huverstuhl ◽  
Dominik Brors

1997 ◽  
Vol 77 (3) ◽  
pp. 1294-1305 ◽  
Author(s):  
Zun-Li Mo ◽  
Robin L. Davis

Mo, Zun-Li and Robin L. Davis. Endogenous firing patterns of murine spiral ganglion neurons. J. Neurophysiol. 77: 1294–1305, 1997. Current-clamp recordings with the use of the whole cell configuration of the patch-clamp technique were made from postnatal mouse spiral ganglion neurons in vitro. Cultures contained neurons that displayed monopolar, bipolar, and pseudomonopolar morphologies. Additionally, a class of neurons having exceptionally large somata was observed. Frequency histograms of the maximum number of action potentials fired from 240-ms step depolarizations showed that neurons could be classified as either slowly adapting or rapidly adapting. Most neurons (85%) were in the rapidly adapting category (58 of 68 recordings). Measurements of elementary properties were used to define the endogenous firing characteristics of both neuron classes. Action potential number varied with step and holding potential, spike amplitude decayed during prolonged depolarizations, and spike frequency adaptation was observed in both rapidly and slowly adapting neurons. The apparent input resistance, spike amplitude decrement, and instantaneous firing frequency differed significantly between rapidly and slowly adapting neurons. Inward rectification was evaluated in response to hyperpolarizing constant current injections. Present in both electrophysiological classes, its magnitude was graded from neuron to neuron, reflecting differences in number, type, and/or voltage dependence of the underlying channels. These data suggest that spiral ganglion neurons possess intrinsic firing properties that regulate action potential number and timing, features that may be crucial to signal coding in the auditory periphery.


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