Daudet N, Vago P, Ripoll C, Humbert G, Pujol R, Lenoir M
INSERM U 254, Université Montpellier I, Faculté de Médecine, France.
J Comp Neurol. 1998 Nov 16;401(2):145-62.
Hair cell regeneration is well documented in the inner ear sensory epithelia of lower vertebrates and birds and may occur in the vestibular organs of mammals. By contrast, hair cell loss in the mature mammalian cochlea is considered irreversible. However, recent reports have suggested that an attempt at hair cell regeneration could occur in vivo in aminoglycoside-lesioned cochleas from neonatal rats. After amikacin treatment, atypical cells with apical specialization reminiscent of early differentiating stereocilia are transiently present at the apex of the intoxicated cochleas but fail to differentiate as hair cells in later stages. In the present study, we used electronic microscopy, histochemistry, and confocal microscopy to investigate the cellular rearrangements in the amikacin-lesioned organ of Corti of rat pups. In addition, we used 5-bromo-2'-deoxyuridine immunocytochemistry to determine whether mitotic processes are involved in the formation of the atypical cells. The morphologic and molecular data suggest that atypical cells are not recovering hair cells, but share characteristics of immature hair cells and supporting cells. Proliferative cells were absent from the region occupied by atypical cells, suggesting that the latter did not arise through mitotic processes. Altogether, the present results support the hypothesis that atypical cells arise through direct transformation of some of the supporting cells that reorganize during hair cell degeneration.
毛细胞再生在低等脊椎动物和鸟类的内耳感觉上皮中已有充分记录,并且可能发生在哺乳动物的前庭器官中。相比之下,成熟哺乳动物耳蜗中的毛细胞损失被认为是不可逆的。然而,最近的报告表明,新生大鼠经氨基糖苷类损伤的耳蜗在体内可能会尝试进行毛细胞再生。用阿米卡星治疗后,在中毒耳蜗的顶端短暂出现具有顶端特化、类似于早期分化静纤毛的非典型细胞,但在后期未能分化为毛细胞。在本研究中,我们使用电子显微镜、组织化学和共聚焦显微镜来研究幼鼠经阿米卡星损伤的柯蒂氏器中的细胞重排。此外,我们使用5-溴-2'-脱氧尿苷免疫细胞化学来确定有丝分裂过程是否参与非典型细胞的形成。形态学和分子数据表明,非典型细胞不是再生的毛细胞,而是具有未成熟毛细胞和支持细胞的特征。非典型细胞占据的区域没有增殖细胞,这表明后者不是通过有丝分裂过程产生的。总之,目前的结果支持这样的假设,即非典型细胞是通过在毛细胞退化过程中重新组织的一些支持细胞的直接转化而产生的。