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耳蜗神经元中外周蛋白表达的新见解。

New insights into peripherin expression in cochlear neurons.

作者信息

Lallemend F, Vandenbosch R, Hadjab S, Bodson M, Breuskin I, Moonen G, Lefebvre P P, Malgrange B

机构信息

Research Center for Cellular and Molecular Neurobiology, Developmental Neurobiology Unit, University of Liège, Av. de l'Hopital 1 (B36), 4000 Liège, Belgium.

出版信息

Neuroscience. 2007 Nov 30;150(1):212-22. doi: 10.1016/j.neuroscience.2007.08.032. Epub 2007 Sep 21.

Abstract

Peripherin is an intermediate filament protein that is expressed in peripheral and enteric neurons. In the cochlear nervous system, peripherin expression has been extensively used as a differentiation marker by preferentially labeling the type II neuronal population at adulthood, but yet without knowing its function. Since the expression of peripherin has been associated in time with the process of axonal extension and during regeneration of nerve fibers in other systems, it was of interest to determine whether peripherin expression in cochlear neurons was a static phenotypic trait or rather prone to modifications following nerve injury. In the present study, we first compared the expression pattern of peripherin and beta III-tubulin from late embryonic stages to the adult in rat cochlea. The staining for both proteins was seen before birth within all cochlear neurons. By birth, and for 2 or 3 days, peripherin expression was gradually restricted to the type II neuronal population and their projections. In contrast, from postnatal day (P) 10 onwards, while the expression of beta III-tubulin was still found in projections of all cochlear neurons, only the type I population had beta III-tubulin immunoreactivity in their cell bodies. We next investigated the expression of peripherin in axotomized cochlear neurons using an organotypic explant model. Peripherin expression was surprisingly re-expressed in a vast majority of neurons after axotomy. In parallel, the expression and localization of beta III-tubulin and peripherin in dissociated cultures of cochlear neurons were studied. Both proteins were distributed along the entire neuronal length but exhibited complementary distribution, especially within the projections. Moreover, peripherin immunoreactivity was still abundant in the growth cone, whereas that of beta III-tubulin was decreasing at this compartment. Our findings are consistent with a model in which peripherin plays an important structural role in cochlear neurons and their projections during both development and regenerative processes and which is compatible with the assumption that frequently developmentally regulated factors are reactivated during neuronal regeneration.

摘要

外周蛋白是一种中间丝蛋白,在外周神经元和肠神经元中表达。在耳蜗神经系统中,外周蛋白的表达已被广泛用作分化标志物,成年期优先标记II型神经元群体,但尚不清楚其功能。由于外周蛋白的表达在时间上与轴突延伸过程以及其他系统中神经纤维再生过程相关,因此确定耳蜗神经元中外周蛋白的表达是一种静态表型特征还是在神经损伤后容易发生改变,这一点很有意义。在本研究中,我们首先比较了大鼠耳蜗从胚胎后期到成年期外周蛋白和βIII微管蛋白的表达模式。在出生前,所有耳蜗神经元中都能看到这两种蛋白的染色。出生时及出生后2或3天,外周蛋白的表达逐渐局限于II型神经元群体及其投射。相比之下,从出生后第10天起,虽然在所有耳蜗神经元的投射中仍能发现βIII微管蛋白的表达,但只有I型神经元群体的细胞体中有βIII微管蛋白免疫反应性。接下来,我们使用器官型外植体模型研究了切断轴突的耳蜗神经元中外周蛋白的表达。令人惊讶的是,切断轴突后,绝大多数神经元中重新表达了外周蛋白。同时,研究了耳蜗神经元解离培养物中βIII微管蛋白和外周蛋白的表达及定位。这两种蛋白都沿神经元全长分布,但呈现互补分布,尤其是在投射部位。此外,外周蛋白免疫反应性在生长锥中仍然丰富,而βIII微管蛋白在这个区域的免疫反应性正在降低。我们的研究结果与这样一种模型一致,即外周蛋白在发育和再生过程中在耳蜗神经元及其投射中发挥重要结构作用,并且与神经元再生过程中经常重新激活发育调控因子的假设相符。

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