Expression of TrkB and BDNF in human cochlea—an immunohistochemical study

Liu, Wei; Kinnefors, Anders; Boström, Marja; Rask‐Andersen, Helge

doi:10.1007/s00441-011-1209-3

Cited by 25 publications

(39 citation statements)

References 34 publications

(41 reference statements)

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“…Earlier research from our group using fetal human cochleae showed BDNF immuno-staining at GW 12 but not in previous stages (Pechriggl et al 2015). In addition, BDNF localization was not observed in immuno-stained cochlear sections from human adults (Liu et al 2011). These findings are not in line with our present data, where ISH clearly demonstrated BDNF expression in both fetuses (GW 9-12) and adults.…”

Section: Discussioncontrasting

confidence: 99%

“…TrkB expression was also evident in the spiral ganglion cells of the developing inner ear at GW 11. This finding parallels previous immuno-histochemical examinations of adult human cochleae revealing TrkB expression being localized in spiral ganglion neurons (Liu et al 2011).…”

Section: Discussionsupporting

confidence: 90%

“…In the adult human inner ear, the expression of p75NTR was identified in the glial cells including Schwann cells and satellite glial cells in the Rosenthal canal, in the central nerve bundles within the modiolus and in the osseous spiral lamina of the human cochleae (Liu et al 2011). However, the role of this receptor during human inner ear development is still a matter of discussion.…”

Section: Introductionmentioning

confidence: 99%

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Role of BDNF and neurotrophic receptors in human inner ear development

et al. 2017

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The expression patterns of the neurotrophin, brain-derived neurotrophic factor, BDNF, and the neurotrophic receptors-p75NTR and Trk receptors-in the developing human fetal inner ear between the gestational weeks (GW) 9 to 12 are examined via in situ hybridization and immunohistochemistry. BDNF mRNA expression was highest in the cochlea at GW 9 but declined in the course of development. In contrast to embryonic murine specimens, a decline in BDNF expression from the apical to the basal turn of the cochlea could not be observed. p75NTR immunostaining was most prominent in the nerve fibers that penetrate into the sensory epithelia of the cochlea, the urticule and the saccule as gestational age progresses. TrkB and TrkC expression intensified towards GW 12, at which point the BDNF mRNA localization was at its lowest. TrkA expression was limited to fiber subpopulations of the facial nerve at GW 10. In the adult human inner ear, we observed BDNF mRNA expression in the apical poles of the cochlear hair cells and supporting cells, while in the adult human utricle, the expression was localized in the vestibular hair cells. We demonstrate the highly specific staining patterns of BDNF mRNA and its putative receptors over a developmental period in which multiple hearing disorders are manifested. Our findings suggest that BDNF and neurotrophin receptors are important players during early human inner ear development. In particular, they seem to be important for the survival of the afferent sensory neurons.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Role of BDNF and neurotrophic receptors in human inner ear development

et al. 2017

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“…The specificity of the polyclonal antibody for p75 NTR was also verified in previous Western blotting (Weskamp and Reichardt 1991;Bitsche et al 2011). Here, we used TrkB to demark the neurons because our previous study has proved that TrkB is a reliable marker for human spiral ganglion neurons and its specificity was clarified in our report (Liu et al 2011). The results of the negative staining in our antibody control ruled out the possibility of a direct staining by reagents other than the primary p75 NTR antibodies.…”

Section: Tissue Preservation and Antibody Specificitymentioning

confidence: 82%

“…Nevertheless, these studies have been mostly carried out in animals and a few in human fetuses (Vega et al 1999). Even though some data on the expression of neurotrophic substances in adult human cochlea have been achieved (Liu et al 2011), our picture in humans is still far from complete.…”

Section: Introductionmentioning

confidence: 99%

Distribution of P75 neurotrophin receptor in adult human cochlea—an immunohistochemical study

et al. 2012

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Mechanisms underlying the unique survival property of human spiral neurons are yet to be explored. P75 (p75(NTR)) is a low affinity receptor for neurotrophins and is known to interact with Trk receptors to modulate ligand binding and signaling. Up-regulation of this receptor was found to be associated with apoptosis as well as with cell proliferation. Its distribution and injury-induced change in expression pattern in the cochlea have been mainly studied in rodents. There is still no report concerning p75(NTR) in post-natal human inner ear. We analyzed, for the first time, p75(NTR) expression in five freshly fixed human cochleae by using immunohistochemistry techniques, including myelin basic protein (MBP) as a myelin sheath marker and TrkB as the human spiral neuron marker, and by using thin optical sectioning of laser confocal microscopy. The inner ear specimens were obtained from adult patients who had normal pure tone thresholds before the surgical procedures, via a trans-cochlear approach for removal of giant posterior cranial fossa meningioma. The expression of p75(NTR) was investigated and localized in the glial cells, including Schwann cells and satellite glial cells in the Rosenthal canal, in the central nerve bundles within the modiolus, and in the osseous spiral lamina of the human cochleae. The biological significance of p75(NTR) in human cochlea is discussed.

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Human Cochlea: Anatomical Characteristics and their Relevance for Cochlear Implantation

Rask‐Andersen

Liu

Erixon

et al. 2012

The Anatomical Record

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This is a review of the anatomical characteristics of human cochlea and the importance of variations in this anatomy to the process of cochlear implantation (CI). Studies of the human cochlea are essential to better comprehend the physiology and pathology of man's hearing. The human cochlea is difficult to explore due to its vulnerability and bordering capsule. Inner ear tissue undergoes quick autolytic changes making investigations of autopsy material difficult, even though excellent results have been presented over time. Important issues today are novel inner ear therapies including CI and new approaches for inner ear pharmacological treatments. Inner ear surgery is now a reality, and technical advancements in the design of electrode arrays and surgical approaches allow preservation of remaining structure/function in most cases. Surgeons should aim to conserve cochlear structures for future potential stem cell and gene therapies. Renewal interest of round window approaches necessitates further acquaintance of this complex anatomy and its variations. Rough cochleostomy drilling at the intricate ''hook'' region can generate intracochlear bone-dust-inducing fibrosis and new bone formation, which could negatively influence auditory nerve responses at a later time point. Here, we present macro-and microanatomic investigations of the human cochlea viewing the extensive anatomic variations that influence electrode insertion. In addition, electron microscopic (TEM and SEM) and immunohistochemical results, based on specimens removed at surgeries for lifethreatening petroclival meningioma and some well-preserved postmortal tissues, are displayed. These give us new information about structure as well as protein and molecular expression in man. Our aim was not to formulate a complete description of the complex human anatomy but to focus on aspects clinically relevant for electric stimulation, predominantly, the sensory targets, and how surgical atraumaticity best could be reached.

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Expression of TrkB and BDNF in human cochlea—an immunohistochemical study

Cited by 25 publications

References 34 publications

Role of BDNF and neurotrophic receptors in human inner ear development

Role of BDNF and neurotrophic receptors in human inner ear development

Distribution of P75 neurotrophin receptor in adult human cochlea—an immunohistochemical study

Human Cochlea: Anatomical Characteristics and their Relevance for Cochlear Implantation

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