Differential expression of trkB.T1 and trkB.T2, truncated trkC, and p75NGFR in the cochlea prior to hearing function

Gestwa, Glikeria; Wiechers, B Ludlow; Zimmermann, Ulrike; Praetorius, Mark; Rohbock, Karin; Köpschall, Iris; Zenner, Hans‐Peter; Knipper, Marlies

doi:10.1002/(sici)1096-9861(19991108)414:1<33::aid-cne3>3.0.co;2-m

Cited by 52 publications

(45 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, NT-3 binding to TrkA receptors in sympathetic ganglia is downregulated by enhanced p75NTR, whereas NGF binding to the same high-affinity receptor is unaffected by the presence of p75NTR (Kuruvilla et al, 2004). These types of complex interactions are also likely in the spiral ganglion where multiple forms of the trkB and trkC receptors have been identified (Gestwa et al, 1999), autocrine mechanisms are present (Hansen et al, 2001), and BDNF, NT-3, and trkB receptor gene expression is tonotopically distributed (Fritzsch et al, 1997;Schimmang et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…A number of studies have shown that during development, this is, in fact, the case. In addition to p75NTR, spiral ganglion neurons possess both trkB and trkC high-affinity tyrosine kinase receptors (Ylikoski et al, 1993;Mou et al, 1997;Cochran et al, 1999;Gestwa et al, 1999). It is possible, therefore, that at higher concentrations (Ͼ10 ng/ml), NT-3 could bind to the trkB receptor in addition to the trkC receptor (Kuruvilla et al, 2004), thus evoking unique electrophysiological characteristics.…”

Section: Discussionmentioning

confidence: 99%

“…Chronic exposure to brainderived neurotrophic factor (BDNF) caused neurons to fire with faster accommodation and kinetics, whereas neurotrophin-3 (NT-3) had the opposite effect (Adamson et al, 2002a). These data suggest that the firing patterns may result from differing levels of neurotrophins and/or tyrosine kinase (trk) receptors (Davis, 2003), a hypothesis supported by the presence of both trkB and trkC high-affinity trk receptors in the spiral ganglion (Ylikoski et al, 1993;Mou et al, 1997;Cochran et al, 1999;Gestwa et al, 1999) and graded NT-3, BDNF, and trkB levels in the adult cochlea and spiral ganglion neurons, respectively (Fritzsch et al, 1997;Schimmang et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Complex Regulation of Spiral Ganglion Neuron Firing Patterns by Neurotrophin-3

Zhou

Liu²,

Davis³

2005

J. Neurosci.

View full text Add to dashboard Cite

Auditory information is conveyed into the CNS via the spiral ganglion neurons, cells that possess distinctive electrophysiological properties that vary according to their cochlear innervation. Neurons from the base of the cochlea fire action potentials with shorter latencies and durations with more rapid accommodation than apical neurons (Adamson et al., 2002b). Interestingly, these features are altered by exposure to brain-derived neurotrophic factor and neurotrophin-3 (NT-3), suggesting that the electrophysiological diversity is not preprogrammed into the neurons but instead results from extrinsic regulation. In support of this, gradients of neurotrophins exist in the cochlea that could account for the apex-base differences in firing. To understand the determinants of spiral ganglion function, we characterized the NT-3 concentration dependence and mode of action on spiral ganglion neurons. Whole-cell current-clamp recordings were made from mouse basal spiral ganglion neurons (postnatal day 5) exposed to different concentrations of NT-3 for 3 d in vitro. Measurements of accommodation, latency, onset time course, and action potential latency revealed a nonmonotonic dependence on NT-3 concentration, with a peak effect occurring at 10 ng/ml. Addition of NT-3 at different time points showed that neurotrophin exposure altered the firing features of existing neurons rather than supporting differential survival. These experiments establish that the electrophysiological phenotype of spiral ganglion neurons depends critically on the precise concentration of NT-3 and that the functional organization of this component of the peripheral auditory system results from a complex interplay between multiple kinds of neurotrophins and their cognate receptors.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Complex Regulation of Spiral Ganglion Neuron Firing Patterns by Neurotrophin-3

Zhou

Liu²,

Davis³

2005

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…To determine the effects of Fgf signaling on the cytoskeleton, cochleae were treated with either Fgf2, which has been shown to bind and activate Fgf receptors, or SU5402, which blocks all Fgf receptors (Mohammadi et al, 1997). An antibody raised to p75 neurotrophin receptor (p75 ntr ) was used to identify differentiated PCs, and previous studies have shown a high correlation between increased p75 ntr expression and decreased actin-mediated cell growth (Gestwa et al, 1999;Deponti et al, 2009). Confocal images at P0 and P3 showed increased p75 ntr immunofluorescence in supporting cells and decreased phalloidin intensity with Fgf2 treatment, but decreased p75 ntr immunofluorescence and increased phalloidin intensity with SU5402 treatment (Fig.…”

Section: Research Articlementioning

confidence: 95%

Cytoskeletal changes in actin and microtubules underlie the developing surface mechanical properties of sensory and supporting cells in the mouse cochlea

et al. 2012

View full text Add to dashboard Cite

SUMMARYCorrect patterning of the inner ear sensory epithelium is essential for the conversion of sound waves into auditory stimuli. Although much is known about the impact of the developing cytoskeleton on cellular growth and cell shape, considerably less is known about the role of cytoskeletal structures on cell surface mechanical properties. In this study, atomic force microscopy (AFM) was combined with fluorescence imaging to show that developing inner ear hair cells and supporting cells have different cell surface mechanical properties with different developmental time courses. We also explored the cytoskeletal organization of developing sensory and non-sensory cells, and used pharmacological modulation of cytoskeletal elements to show that the developmental increase of hair cell stiffness is a direct result of actin filaments, whereas the development of supporting cell surface mechanical properties depends on the extent of microtubule acetylation. Finally, this study found that the fibroblast growth factor signaling pathway is necessary for the developmental time course of cell surface mechanical properties, in part owing to the effects on microtubule structure.

show abstract

“…Northern Blot Analysis of Tectorin mRNA-Northern blot analysis was performed as described recently (6,22,27). The effect of TH on mRNA levels was evaluated and semiquantified using mRNAs isolated from a similar number of cochleae as described previously (22).…”

Section: Methodsmentioning

confidence: 99%

Thyroid Hormone-deficient Period Prior to the Onset of Hearing Is Associated with Reduced Levels of β-Tectorin Protein in the Tectorial Membrane

Knipper¹,

Richardson²,

Mack³

et al. 2001

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The genes for ␣-and ␤-tectorin encode the major noncollagenous proteins of the tectorial membrane. Recently, a targeted deletion of the mouse ␣-tectorin gene was found to cause loss of cochlear sensitivity (1). Here we describe that mRNA levels for ␤-tectorin, but not ␣-tectorin, are significantly reduced in the cochlear epithelium under constant hypothyroid conditions and that levels of ␤-tectorin protein in the tectorial membrane are lower. A delay in the onset of thyroid hormone supply prior to onset of hearing, recently described to result in permanent hearing defects and loss of active cochlear mechanics (2), can also lead to permanently reduced ␤-tectorin protein levels in the tectorial membrane. ␤-Tectorin protein levels remain low in the tectorial membrane up to one year after the onset of thyroid hormone supply has been delayed until postnatal day 8 or later and are associated with an abnormally structured tectorial membrane and the loss of active cochlear function. These data indicate that a simple delay in thyroid hormone supply during a critical period of development can lead to low ␤-tectorin levels in the tectorial membrane and suggest for the first time that ␤-tectorin may be required for development of normal hearing.It has been known for many years that thyroid hormone (TH) 1 is necessary for normal development of the auditory system (3-5). Both genetic and acquired neonatal TH deficiency may result in a profound mental disability that is often accompanied by deafness. The existence of various TH-sensitive periods during inner ear development and the success of delayed, corrective TH treatment has recently been investigated (2, 6). These studies revealed that maternal TH prior to the onset of thyroid gland function, as well as TH supply beyond the onset of hearing at postnatal day 12 (P12), was not critical for the development of normal hearing in rats (2, 6). However, within the crucial period of time any delay in the rise of TH plasma levels (transient hypothyroidism) leads to permanent hearing defects, though the organ of Corti develops to an organ without obvious structural or neuronal abnormalities (2). Analysis of distortion product otoacoustic emissions revealed that the active cochlear process was TH-dependent and was permanently lost following the induction of a transient TH-free period between E17 and ϾP8 (2). Distortion product otoacoustic emissions are sounds that emanate from the ear and are believed to be produced by the interaction of actively amplified traveling waves on the basilar membrane (7-9). The tectorial membrane plays a crucial role in this active process, because it couples transverse, sound-induced, basilar membrane motion to a radial deflection of the sensory hair bundles. In former studies with rodents (10, 11) it has been observed that the tectorial membrane is distorted as a result of constant hypothyroidism. The major non-collagenous components of the tectorial membrane, ␣-and ␤-tectorin, were identified recently as the products of single copy genes (12). Missen...

show abstract

Differential expression of trkB.T1 and trkB.T2, truncated trkC, and p75NGFR in the cochlea prior to hearing function

Cited by 52 publications

References 88 publications

Complex Regulation of Spiral Ganglion Neuron Firing Patterns by Neurotrophin-3

Complex Regulation of Spiral Ganglion Neuron Firing Patterns by Neurotrophin-3

Cytoskeletal changes in actin and microtubules underlie the developing surface mechanical properties of sensory and supporting cells in the mouse cochlea

Thyroid Hormone-deficient Period Prior to the Onset of Hearing Is Associated with Reduced Levels of β-Tectorin Protein in the Tectorial Membrane

Contact Info

Product

Resources

About