Type III intermediate filament peripherin inhibits neuritogenesis in type II spiral ganglion neurons in vitro
Type III intermediate filament peripherin inhibits neuritogenesis in type II spiral ganglion neurons in vitro
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DOI：
10.1016/j.neulet.2010.01.063
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发表时间：
2010-07-05
影响因子：
2.5
通讯作者：
Housley, Gary D.
中科院分区：
文献类型：
--
作者：
Barclay, Meagan;Julien, Jean-Pierre;Housley, Gary D.
外周蛋白是一种III型中间丝蛋白，在神经元的一个子集中形成细胞骨架的一部分，其中大多数神经元有外周纤维投射。研究表明，外周蛋白在轴突生长和再生中发挥了作用，但在感觉和脑组织中这一点的证据有限。由于外周蛋白在初级听神经细胞亚群--II型螺旋神经节神经元中的独有表达，促使我们研究外周蛋白基因缺失(PphKO)对这些神经元的影响。我们用共聚焦免疫荧光技术检测了生后1周内，在野生型(WT)和pphKO小鼠中，II型SGN神经突起在体内外对耳蜗外毛细胞的支配作用。耳蜗II型SGN神经纤维在pphKO耳蜗内呈正常分布。然而，在大多数轴突来源于II型SGN的培养条件下，使用P1螺旋神经节外植体，pphKO导致与WT对照组相比，轴突/外植体的数量增加。来自pphKO外植体的II型SGN神经突起延伸的距离类似于WT神经突起的两倍，并且由于转折点之间的距离较大而降低了复杂性。在WT和KO外植体中添加脑源性神经营养因子(BDNF)可使轴突数目增加约30倍，但不影响轴突的长度和旋转距离。这些结果表明，外周蛋白可能与其他细胞骨架元素相互作用，调节II型SGN外周神经突起的生长，从而将这些神经元与支配内毛细胞的I型SGN区分开来。(C)2010爱思唯尔爱尔兰有限公司。保留所有权利。
Peripherin, a type III intermediate filament protein, forms part of the cytoskeleton in a subset of neurons, most of which have peripheral fibre projections. Studies suggest a role for peripherin in axon outgrowth and regeneration, but evidence for this in sensory and brain tissues is limited. The exclusive expression of peripherin in a sub-population of primary auditory neurons, the type II spiral ganglion neurons (SGN) prompted our investigation of the effect of peripherin gene deletion (pphKO) on these neurons. We used confocal immunofluorescence to examine the establishment of the innervation of the cochlear outer hair cells by the type II SGN neurites in vivo and in vitro, in wildtype (WT) and pphKO mice, in the first postnatal week. The distribution of the type II SGN nerve fibres was normal in pphKO cochleae. However, using P1 spiral ganglion explants under culture conditions where the majority of neurites were derived from type II SGN, pphKO resulted in increased numbers of neurites/explant compared to WT controls. Type II SGN neurites from pphKO explants extended similar to double the distance of WT neurites, and had reduced complexity based on greater distance between turning points. Addition of brain-derived neurotrophic factor (BDNF) to the culture media increased neurite number in WT and KO explants similar to 30-fold, but did not affect neurite length or distance between turning. These results indicate that peripherin may interact with other cytoskeletal elements to regulate outgrowth of the peripheral neurites of type II SGN, distinguishing these neurons from the type I SGN innervating the inner hair cells. (C) 2010 Elsevier Ireland Ltd. All rights reserved.