Intranasal administration of rotenone in mice attenuated olfactory functions through the lesion of dopaminergic neurons in the olfactory bulb
Intranasal administration of rotenone in mice attenuated olfactory functions through the lesion of dopaminergic neurons in the olfactory bulb
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DOI：
10.1016/j.neuro.2015.10.006
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发表时间：
2015-12-01
期刊：
影响因子：
3.4
通讯作者：
Kashiwayanagi, Makoto
中科院分区：
文献类型：
--
作者：
Sasajima, Hitoshi;Miyazono, Sadaharu;Kashiwayanagi, Makoto
许多环境化学物质被认为会影响大脑功能。据报道，鼻腔中的化学物质通过嗅觉神经元和嗅球（OB）之间的连接直接到达大脑。在这种“嗅觉运输”中，在鼻黏膜吸收的外来生物绕过一些物理屏障和防御到达大脑，因此嗅觉运输被怀疑是大脑抵御环境化学物质入侵威胁的脆弱机制。在这项研究中，我们重点研究了鱼藤酮鼻内给药对小鼠的神经元毒性。结果表明，给予鱼藤酮的小鼠嗅觉功能减弱。我们还发现，鼻内给药鱼藤酮可诱导OB的急性线粒体应激。重复给药鱼藤酮导致OB中多巴胺能神经元数量减少，多巴胺能神经元是OB中的抑制性中间神经元。综上所述，我们的研究结果表明，吸入环境毒素可通过嗅觉运输诱导颅神经元的神经变性。嗅觉功能障碍可能是由吸入神经毒素引起的神经变性的早期症状。(C) 2015爱思唯尔公司版权所有。
Many environmental chemicals are thought to affect brain function. It was reported that chemicals-in the nasal cavity directly reach the brain through the connection between olfactory neurons and the olfactory bulb (OB). In this 'olfactory transport,' xenobiotics absorbed at the nasal mucosa reach the brain by bypassing some physical barriers and defenses, and thus olfactory transport is suspected to be a vulnerable mechanism of the brain against invasion threats of environmental chemicals. In this study, we focused on the neuronal toxicity of rotenone administered intranasally to mice. The results showed that the mice that were administered rotenone had attenuated olfactory functions. We also found that intranasally administered rotenone induced acute mitochondrial stress at the OB. The repeated administration of rotenone resulted in a decrease in the number of dopaminergic neurons, which are inhibitory interneurons in the OB. Taken together, our findings suggest that the inhalation of environmental toxins induces the neurodegeneration of cranial neurons through olfactory transport, and that olfactory dysfunction may be induced as an earliest symptom of neurodegeneration caused by inhaled neurotoxins. (C) 2015 Elsevier Inc. All rights reserved.