Staecker H, Galinovic-Schwartz V, Liu W, Lefebvre P, Kopke R, Malgrange B, Moonen G, Van De Water T R
Department of Otolaryngology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Am J Otol. 1996 May;17(3):486-92.
Auditory hair cells produce trophic factors that directly affect maturation and survival of auditory neurons. These factors include two members of the neurotrophin family: brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). Loss of hair cells, as a result of either noise trauma or ototoxic damage, results in the degeneration of auditory neurons. An in vitro model of early postnatal rat organ of Corti/spiral ganglion explants was used to study the effects of deprivation and supplementation of nerve growth factor (NGF), BDNF, and NT-3 on neuronal survival. Immunolocalization of receptors for these neurotrophins correlated with their effectiveness as promoters of neuronal survival. BDNF affected early neuronal survival, whereas NT-3 was the most important survival factor for maturing auditory neurons. NGF was shown to maintain axonal morphology. Our results support the hypothesis that changes in the expression of these neurotrophins and their specific receptors in the maturing cochlea may control the postnatal processes of neuronal apoptosis and maturation of the innervation of both inner and outer hair cells. The results suggest that these growth factors have potential for preventing neuronal degeneration as well as enhancing the repair of damaged neuronal processes in the traumatized auditory system.
听觉毛细胞产生的营养因子直接影响听觉神经元的成熟和存活。这些因子包括神经营养因子家族的两个成员:脑源性神经营养因子(BDNF)和神经营养因子-3(NT-3)。由于噪声损伤或耳毒性损伤导致的毛细胞缺失会导致听觉神经元的退化。利用新生大鼠耳蜗/螺旋神经节外植体的体外模型研究了神经生长因子(NGF)、BDNF和NT-3的剥夺和补充对神经元存活的影响。这些神经营养因子受体的免疫定位与其作为神经元存活促进剂的有效性相关。BDNF影响早期神经元存活,而NT-3是成熟听觉神经元最重要的存活因子。已证明NGF可维持轴突形态。我们的结果支持这样一种假说,即这些神经营养因子及其特异性受体在成熟耳蜗中的表达变化可能控制出生后神经元凋亡过程以及内外毛细胞神经支配的成熟。结果表明,这些生长因子具有预防神经元退化以及促进受创伤听觉系统中受损神经元过程修复的潜力。