Department of Veterinary Anatomy, College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, 102 Jejudaehakno, Jeju, 63243, Republic of Korea.
Veterinary Medical Research Institute, Jeju National University, Jeju, 63243, Republic of Korea.
Mol Neurobiol. 2018 Nov;55(11):8499-8508. doi: 10.1007/s12035-018-1001-4. Epub 2018 Mar 20.
Olfactory dysfunction is an early sign of neuroinflammation of the central nervous system (CNS). Microgliosis and astrogliosis are representative pathological changes that develop during neuroinflammation of CNS tissues. Autoimmune CNS inflammation, including human multiple sclerosis, is an occasional cause of olfactory disorders. We evaluated whether gliosis and olfactory dysfunction developed in animals with experimental autoimmune encephalomyelitis (EAE), a model of human multiple sclerosis. Neuroinflammatory lesions characterized by infiltration of inflammatory cells and microglial cell activation were occasionally found in the olfactory bulbs of EAE-affected rats. Microglial activation, visualized by immunohistochemical staining of ionized calcium binding protein (Iba)-1, and astrogliosis in the olfactory bulb were also evident in the olfactory bulb of EAE rats. Inflammatory cells were found along the olfactory nerves and in the olfactory submucosa. Western blot analysis of olfactory marker protein (OMP) levels showed that OMP expression was significantly downregulated in the olfactory mucosa of EAE rats. On the buried food test, EAE-affected mice required significantly more time to find a bait pellet. Collectively, the results suggest that the olfactory dysfunction of EAE is closely linked to downregulation of OMP and the development of inflammatory foci in the olfactory system in an animal model of human multiple sclerosis.
嗅觉功能障碍是中枢神经系统（CNS）神经炎症的早期迹象。小胶质细胞增生和星形胶质细胞增生是 CNS 组织神经炎症过程中出现的代表性病理变化。自身免疫性 CNS 炎症，包括人类多发性硬化症，是引起嗅觉障碍的偶尔原因。我们评估了实验性自身免疫性脑脊髓炎（EAE）动物是否会出现神经炎症和嗅觉功能障碍，EAE 是人类多发性硬化症的模型。在受 EAE 影响的大鼠嗅球中偶尔会发现以炎性细胞浸润和小胶质细胞激活为特征的神经炎症性病变。在 EAE 大鼠的嗅球中，还可以通过离子钙结合蛋白（Iba-1）的免疫组织化学染色观察到小胶质细胞激活和星形胶质细胞增生。炎性细胞沿着嗅神经和嗅黏膜下存在。嗅黏膜蛋白（OMP）水平的 Western blot 分析显示，EAE 大鼠嗅黏膜中的 OMP 表达显著下调。在埋藏食物测试中，受 EAE 影响的小鼠需要更多的时间才能找到诱饵颗粒。综上所述，这些结果表明，EAE 的嗅觉功能障碍与 OMP 的下调以及人类多发性硬化症动物模型中嗅觉系统炎症灶的发展密切相关。
