Neuritenwachstum in vitro durch BDNF und GDNF in Kombination mit Dexamethason auf kultivierte Spiralganglienzellen

Stöver, Timo; Scheper, Verena; Diensthuber, Marc; Lenarz, Thomas; Wefstaedt, Patrick

doi:10.1055/s-2006-945005

Cited by 8 publications

(3 citation statements)

References 17 publications

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“…These observations are akin to those of others in SGNs (Stöver et al, 2007; Wefstaedt et al, 2005; Wei et al, 2007) and other neuronal cell types (Ledda et al, 2002; Paratcha et al, 2001); e.g. Wefstaedt et al (2005) found that 100 ng/ml of GDNF increased the number of neurite-bearing SGNs in dissociated neuron cultures.…”

Section: Discussionsupporting

confidence: 80%

“…However, early postnatal SGNs were not used in this study and a dose of GDNF (100 pg/ml) was used, being substantially lower than doses that were effective in our hands as well as those of several investigators using other systems (e.g. Hauck et al, 2006; Uchida et al, 2006; Villegas et al, 2006), including SGs of different species (Maruyama et al, 2007; Stöver et al, 2007). Numbers of cell bodies per explant could not be discerned in our explants, being too bulky for visualization of individual structures within.…”

Section: Discussionmentioning

confidence: 99%

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Glial cell line-derived neurotrophic factor (GDNF) induces neuritogenesis in the cochlear spiral ganglion via neural cell adhesion molecule (NCAM)

Euteneuer

Yang

Chávez

et al. 2013

Molecular and Cellular Neuroscience

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Glial cell line-derived neurotrophic factor (GDNF) increases survival and neurite extension of spiral ganglion neurons (SGNs), the primary neurons of the auditory system, via yet unknown signaling mechanisms. In other cell types, signaling is achieved by the GPI-linked GDNF family receptor α1 (GFRα1) via recruitment of transmembrane receptors: Ret (re-arranged during transformation) and/or NCAM (neural cell adhesion molecule). Here we show that GDNF enhances neuritogenesis in organotypic cultures of spiral ganglia from 5-day-old rats and mice. Addition of GFRα1-Fc increases this effect. GDNF/GFRα1-Fc stimulation activates intracellular PI3K/Akt and MEK/Erk signaling cascades as detected by Western blot analysis of cultures prepared from rats at postnatal days 5 (P5, before the onset of hearing) and 20 (P20, after the onset of hearing). Both cascades mediate GDNF stimulation of neuritogenesis, since application of the Akt inhibitor Wortmannin or the Erk inhibitor U0126 abolished GDNF/GFRα1-Fc stimulated neuritogenesis in P5 rats. Since cultures of P5 NCAM-deficient mice failed to respond by neuritogenesis to GDNF/GFRα1-Fc, we conclude that NCAM serves as a receptor for GDNF signaling responsible for neuritogenesis in early postnatal spiral ganglion.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Glial cell line-derived neurotrophic factor (GDNF) induces neuritogenesis in the cochlear spiral ganglion via neural cell adhesion molecule (NCAM)

Euteneuer

Yang

Chávez

et al. 2013

Molecular and Cellular Neuroscience

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“…The results of the present study confirmed that cell-derived human BDNF has a neuroprotective effect on SGN. Several other studies showed an enhanced SGN survival in vitro [13,37,40,45] and in vivo [15,46,47], which was mediated by BDNF. However, an analogous neuritogenesis as determined by measuring the neurite length of SGN was not observed in the herein presented study.…”

Section: Discussionmentioning

confidence: 97%

Effect of hyperbaric oxygen on BDNF-release and neuroprotection: Investigations with human mesenchymal stem cells and genetically modified NIH3T3 fibroblasts as putative cell therapeutics

et al. 2017

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Hyperbaric oxygen therapy (HBOT) is a noninvasive widely applied treatment that increases the oxygen pressure in tissues. In cochlear implant (CI) research, intracochlear application of neurotrophic factors (NTFs) is able to improve survival of spiral ganglion neurons (SGN) after deafness. Cell-based delivery of NTFs such as brain-derived neurotrophic factor (BDNF) may be realized by cell-coating of the surface of the CI electrode. Human mesenchymal stem cells (MSC) secrete a variety of different neurotrophic factors and may be used for the development of a biohybrid electrode in order to release endogenously-derived neuroprotective factors for the protection of residual SGN and for a guided outgrowth of dendrites in the direction of the CI electrode. HBOT could be used to influence cell behaviour after transplantation to the inner ear. The aim of this study was to investigate the effect of HBOT on the proliferation, BDNF-release and secretion of neuroprotective factors. Thus, model cells (an immortalized fibroblast cell line (NIH3T3)–native and genetically modified) and MSCs were repeatedly (3 x – 10 x) exposed to 100% oxygen at different pressures. The effects of HBO on cell proliferation were investigated in relation to normoxic and normobaric conditions (NOR). Moreover, the neuroprotective and neuroregenerative effects of HBO-treated cells were analysed by cultivation of SGN in conditioned medium. Both, the genetically modified NIH3T3/BDNF and native NIH3T3 fibroblasts, showed a highly significant increased proliferation after five days of HBOT in comparison to normoxic controls. By contrast, the number of MSCs was decreased in MSCs treated with 2.0 bar of HBO. Treating SGN cultures with supernatants of fibroblasts and MSCs significantly increased the survival rate of SGN. HBO treatment did not influence (increase / reduce) this effect. Secretome analysis showed that HBO treatment altered the protein expression pattern in MSCs.

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Cochlear implants and drug delivery: In vitro evaluation of dexamethasone release

et al. 2013

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Anti-inflammatory drugs can minimize the trauma and inflammation in the inner ear caused by cochlear implantation surgery. For this reason, much effort has recently been devoted to finding the best way to administer these anti-inflammatory drugs for a prolonged time and in a personalized dosage. One solution is constructing an electrode with a dispenser filled with anti-inflammatory drugs with a dosage adapted to suit each new cochlear implant user. The purpose of this study was to measure in vitro, by high-performance liquid chromatography-mass spectrometry assay, the amount of dexamethasone released in 78 days in a physiological solution by a filled dispenser. The drug release continued for more than 2 months in three different phases: (1) during the first 1-5 days, (2) within about 2 weeks, and (3) from about 3 weeks until the end of experiment. This release trend is in accordance with the 3 main phases of damage caused by the cochlear implantation: (1) insertion trauma within the first 2 days, (2) inflammation within 2 weeks, and finally (3) an intracochlear chronic fibrosis reaction. Future animal model studies should consider using this dispenser in order to establish its effectiveness in preventing damage caused by cochlear implantation.

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Neuritenwachstum in vitro durch BDNF und GDNF in Kombination mit Dexamethason auf kultivierte Spiralganglienzellen

Abstract: Neurite outgrowth induced by neurotrophic factors could not be observed to be reduced when dexamethasone is given at the same time. Therefore the demonstrated results provide a basis for further animal studies in this field of research.

Cited by 8 publications

References 17 publications

Glial cell line-derived neurotrophic factor (GDNF) induces neuritogenesis in the cochlear spiral ganglion via neural cell adhesion molecule (NCAM)

Glial cell line-derived neurotrophic factor (GDNF) induces neuritogenesis in the cochlear spiral ganglion via neural cell adhesion molecule (NCAM)

Effect of hyperbaric oxygen on BDNF-release and neuroprotection: Investigations with human mesenchymal stem cells and genetically modified NIH3T3 fibroblasts as putative cell therapeutics

Cochlear implants and drug delivery: In vitro evaluation of dexamethasone release

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