Department of Otorhinolaryngology, Medical University of Innsbruck, Anichstr. 35, 6020, Innsbruck, Austria.
Department of Anatomy, Histology & Embryology, Division of Clinical & Functional Anatomy, Medical University of Innsbruck, Muellerstrasse 59, 6020, Innsbruck, Austria.
Cell Tissue Res. 2017 Dec;370(3):347-363. doi: 10.1007/s00441-017-2686-9. Epub 2017 Sep 19.
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.
通过原位杂交和免疫组织化学技术,研究了神经生长因子(BDNF)及其受体(p75NTR 和 Trk 受体)在 9 至 12 孕周(GW)人类胎儿内耳发育过程中的表达模式。在 GW9 时,BDNFmRNA 的表达在耳蜗中最高,但在发育过程中逐渐下降。与胚胎鼠标本不同,BDNF 表达从耳蜗的顶部到底部并没有下降的趋势。p75NTR 免疫染色在随着胎龄的增加而逐渐增强,主要集中在穿透耳蜗、耳石和椭圆囊感觉上皮的神经纤维中。TrkB 和 TrkC 的表达在 GW12 时增强,此时 BDNFmRNA 的定位达到最低水平。TrkA 的表达仅限于 GW10 时面神经的纤维亚群。在成人内耳中,我们观察到 BDNFmRNA 在耳蜗毛细胞和支持细胞的顶端表达,而在成人的椭圆囊中,其表达则局限于前庭毛细胞。我们展示了 BDNFmRNA 及其潜在受体在多个听力障碍表现的发育过程中的高度特异性染色模式。我们的研究结果表明,BDNF 和神经营养因子受体在人类内耳早期发育中是重要的参与者。特别是,它们似乎对传入感觉神经元的存活很重要。
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