Apoptosis of inner hair cells caused by laser ablation of their spiral ganglion neurons in cultures of the mouse organ of Corti.
Apoptosis of inner hair cells caused by laser ablation of their spiral ganglion neurons in cultures of the mouse organ of Corti.
复制标题
激光消融小鼠柯蒂氏器官培养物中的螺旋神经节神经元引起的内毛细胞凋亡。
DOI：
10.1023/a:1007086525385
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
August,BK
中科院分区：
文献类型：
--
作者：
Sobkowicz,HM;Slapnick,SM;August,BK
激光束消融的螺旋神经节神经元进行了7个器官型培养的新生小鼠耳蜗在体外5至8天之间，从18小时至3天的恢复期。对毛细胞造成的直接躯体损伤（激光或机械）并不一定会导致它们的死亡;它们中的许多人存活下来，修复损伤并重新建立它们的神经感觉连接。相比之下，激光照射和消融其传入螺旋神经节神经元会在损伤后18-48小时内导致感觉细胞发生最严重的变性。在超微结构上，退化的毛细胞--内毛细胞的特征--显示出“暗细胞空泡变性”，其结合了凋亡性死亡的迹象（核染色质的外周凝聚和核固缩）和细胞水肿、空泡化和坏死的迹象。细胞质的最终浓缩使死细胞呈现出深黑色的外观。照射后螺旋神经节神经元死亡，表现出相似的病理特征。内毛细胞变性的程度和部位与消融的螺旋神经节神经元相对应：最终消融一个神经元会导致传入神经支配的最近径向段内的单个内毛细胞变性。用机械方法消除螺旋神经节神经元并不影响毛细胞的存活，推测激光脉冲作为刺激物，通过过度刺激神经元能受体，使螺旋神经节神经元及其放射状纤维的神经元膜去极化，并引起其突触感觉细胞的兴奋性毒性死亡。传入树突和内毛细胞之间的相互突触前和突触后突触可能作为刺激的入口。这种明显的跨突触诱导的内毛细胞凋亡的发病机制将在培养中进一步研究。
Laser beam ablation of spiral ganglion neurons was performed in seven organotypic cultures of the newborn mouse cochlea between 5 and 8 days in vitro, with a recovery period of from 18 hours to 3 days. Direct somatic injury (laser or mechanical) inflicted on hair cells does not necessarily cause their death; many of them survive, repair damage and re-establish their neurosensory connections. By contrast, laser irradiation and ablation of their afferent spiral ganglion neurons causes a most spectacular degeneration of sensory cells within 18–48 hours after the insult. Ultrastructurally, the degenerated hair cells—characteristically the inner hair cells—display “dark-cell vacuolar degeneration” that combines the signs of apoptotic death (the peripheral condensation of nuclear chromatin and nuclear pyknosis) with signs of cell edema, vacuolization and necrosis. The ultimate condensation of the cytoplasm gives the dead cells a jet black appearance. The irradiated spiral ganglion neurons die displaying similar pathological characteristics. The extent and locus of inner hair cell degeneration correspond to that of ablated spiral ganglion neurons: ultimately the ablation of one neuron causes degeneration of a single inner hair cell within the closest radial segment of the afferent innervation. The elimination of spiral ganglion neurons by mechanical means does not affect hair cell survival.It is inferred that the laser pulse acts as a stimulus depolarizing the neuronal membrane of the spiral ganglion neurons and their radial fibers and causing the excitotoxic death of their synaptic sensory cells through excessive stimulation of the glutamatergic receptors. Reciprocal pre-and postsynaptic synapses between the afferent dendrites and inner hair cells in culture could possibly serve as entryways of the stimulus. The pathogenesis of this apparent transsynaptically-induced apoptotic death of inner hair cells will be further examined in culture.