Nerve growth factor applied onto the olfactory epithelium alleviates degenerative changes of the olfactory receptor neurons following axotomy

Nerve growth factor applied onto the olfactory epithelium alleviates degenerative changes of the olfactory receptor neurons following axotomy
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将神经生长因子应用于嗅觉上皮可减轻轴索切除术后嗅觉受体神经元的退行性变化

DOI:
10.1016/s0006-8993(00)02966-8
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发表时间:
2000
期刊:
影响因子:
2.9
通讯作者:
K. Noguchi
K. Noguchi
中科院分区:
医学3区
文献类型:
--
作者:
H. Yasuno;K. Fukazawa;T. Fukuoka;E. Kondo;M. Sakagami;K. Noguchi

文献摘要

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哺乳动物神经系统的嗅神经上皮在一生中表现出持续的神经发生。最近的研究表明,神经营养因子及其受体可能在嗅觉系统的发育和再生中发挥调节作用。然而,研究外源性神经营养因子在嗅觉系统中的作用的活体研究很少。本研究将神经生长因子(NGF)和脑源性神经营养因子(BDNF)注射于大鼠嗅神经切断后5天的嗅黏膜内。然后,我们研究了外源性神经营养因子对轴突切断后嗅觉感受器神经元退行性变化的影响。进一步,我们检测了它们的受体Trk A和Trk B的位置。我们发现,与生理盐水对照组相比,NGF作用于轴突切除的嗅神经上皮5天后,成熟和未成熟的Orns分别表达更强的嗅觉标记蛋白和β-微管蛋白mRNAs信号。总剂量为10μg的脑源性神经营养因子无此作用。在嗅觉上皮细胞上应用NGF的效果与免疫组织化学结果一致,即Trk A存在于正常和轴突切断的On的树突和轴突束中。这些结果提示,NGF可能通过与嗅觉上皮细胞表面TrkA受体结合来保护成熟和未成熟嗅鞘切断后的退行性改变。
The olfactory neuroepithelium of the mammalian nervous system manifests continuous neurogenesis throughout life. Recent studies suggest that neurotrophic factors and their receptors may play a role in the regulation of development and regeneration in the olfactory system. However, there have been very few in vivo studies investigating the effect of exogenous neurotrophic factors in the olfactory system. In the present study, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were administered into the rat olfactory mucosa for 5 days just after the transection of the olfactory nerve. We then examined the effect of exogenous neurotrophic factors on the degenerative changes in axotomized olfactory receptor neurons (ORNs). Further, we examined the location of their receptors, Trk A and Trk B. We found that both mature and immature ORNs expressed more intense signals for olfactory marker protein and beta-tubulin mRNAs, respectively, when NGF was applied to the axotomized olfactory neuroepithelium for 5 days, compared to the ORNs of saline-treated controls. BDNF at a 10 μg total dose did not show this effect. The effect of NGF applied onto the olfactory epithelium is consistent with the immunohistochemical finding that Trk A was present in the dendrites and axon bundles in normal and axotomized ORNs. These results suggest that NGF may protect the degenerative changes in mature and immature ORNs following axotomy through the binding to the Trk A receptor located on the surface of the olfactory epithelium.