The Impact of Ovariectomy on Olfactory Neuron Regeneration in Mice
The Impact of Ovariectomy on Olfactory Neuron Regeneration in Mice
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DOI：
10.1093/chemse/bjaa005
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发表时间：
2020-03-01
期刊：
影响因子：
3.5
通讯作者：
Miwa, Takaki
中科院分区：
文献类型：
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作者：
Yamada, Kentaro;Shiga, Hideaki;Miwa, Takaki
雌激素已被证明在多种神经系统中作为有丝分裂原影响分化和增殖。嗅觉感受器细胞在神经系统中是独一无二的，即使一个人已经成熟，它也有再生的能力。嗅觉感受器细胞在实验诱导退化后也会再生。本研究旨在观察卵巢切除后雌激素耗竭对嗅神经再生的影响。雌性小鼠于8周龄接受双侧卵巢切除，1周后接受他巴唑的腹腔注射。分别于给药后2、4、6周取嗅黏膜进行组织化学分析，测定嗅觉上皮厚度、嗅觉标志物蛋白分布及Ki-67免疫反应。术后2周，分别用免疫组织化学和酶联免疫吸附试验检测TrkA蛋白在OE中的分布和嗅球中神经生长因子(NGF)的含量。我们的结果显示，在去卵巢的小鼠，注射他巴唑2周后，OMP、Ki-67和TrkA免疫阳性细胞的表达减少，这是一个正在进行再生的时间点。在同一时间点，尽管在给药前嗅球中NGF的产生有所增加，但OVX组和对照组之间没有观察到差异。这些结果表明，雌激素缺乏对嗅觉神经元的再生有抑制作用，雌激素可能在治疗感觉神经性嗅觉功能障碍方面有潜在的用途。
Estrogen has been shown to affect differentiation and proliferation as a mitogen in various neural systems. Olfactory receptor cells are unique within the nervous system, and have the ability to regenerate even after an individual has reached maturity. Olfactory receptor cells also regenerate after experimentally induced degeneration. The purpose of this study is to observe the influence of estrogen depletion induced by ovariectomy on olfactory nerve regeneration. Female mice underwent bilateral ovariectomy at 8 weeks of age and received intraperitoneal administration of methimazole 1 week later. At 2, 4, and 6 weeks after methimazole administration, the olfactory mucosa was analyzed histochemically to determine olfactory epithelium (OE) thickness, olfactory marker protein distribution, and Ki-67 immunoreactivity. Furthermore, 2 weeks after ovariectomy, trkA protein distribution in the OE and nerve growth factor (NGF) levels in the olfactory bulb were determined by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. Our results showed that in ovariectomized mice OMP, Ki-67, and trkA-immunopositive cells expression decreased at 2 weeks after methimazole injection, a time point at which regeneration is underway. At this same time point, although NGF production in the olfactory bulb had increased before methimazole administration, no differences were observed between the ovx and control groups. These results suggest that estrogen depletion induces a suppressive effect on regeneration of olfactory neurons, and that estrogen may have a potential use in the treatment of sensorineural olfactory dysfunction.