Differential effects of olfactory toxicants on olfactory regeneration
Differential effects of olfactory toxicants on olfactory regeneration
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DOI：
10.1007/s00204-002-0321-2
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发表时间：
2002-03-01
影响因子：
6.1
通讯作者：
Brittebo, EB
中科院分区：
文献类型：
--
作者：
Bergman, U;Östergren, A;Brittebo, EB
其目的是研究NMRI小鼠在暴露于嗅觉毒物阿克洛贝尼（一种除草剂）或甲巯咪唑（一种抗甲状腺药物）后嗅觉粘膜的长期反应。在暴露于氯苄腈（2x或1x 25 mg/kg i. p.）后3个月和6个月，嗅区的背内侧部分显示呼吸道化生，伴有大量内陷和纤维化的固有层。相比之下，暴露于毒性剂量的甲巯咪唑（2 × 50 mg/kg i. p.）3个月后，嗅神经上皮和固有层已恢复。为了研究再生事件，我们使用了一种抗生长相关蛋白43（GAP-43）的抗体，这种抗体可以染色未成熟的神经元。为了研究上皮分化和水平基底细胞（HBCs），我们使用了一种抗细胞角蛋白的抗体。他巴唑处理后两周，在整个嗅觉区域中GAP-43染色的细胞显著增加，这与当时观察到的再生相关。两个星期后，在嗅区受损的非典型上皮显示出明显的角蛋白染色的基底和柱状细胞，而GAP-43染色cells wasn 't found. Despite一个短暂的增加GAP-43染色的细胞之间的边界区受损和未受损的嗅粘膜，一个正常的神经上皮细胞扩展到受损的嗅区没有检测到在奥洛贝尼治疗的小鼠。一个完整的固有层被认为是一个先决条件的神经上皮细胞的毒物诱导的损伤后重新种群。
The aim was to study the long-term response in the olfactory mucosa of NMRI mice after exposure to the olfactory toxicants dichlobenil (a herbicide) or methimazole (an antithyroid drug). Three and six months after exposure to dichlobenil (2x or 1x25 mg/kg i.p.), the dorsomedial part of the olfactory region showed a respiratory metaplasia with abundant invaginations and a fibrotic lamina propria. In contrast, 3 months after exposure to a toxic dose of methimazole (2x50 mg/kg i.p.), the olfactory neuroepithelium and lamina propria had been restored. To study the regenerative events, we used an antibody derived against growth-associated protein 43 (GAP-43), which stains immature neurons. To study epithelial differentiation and horizontal basal cells (HBCs) we used an antibody derived against some cytokeratins. Two weeks after methimazole treatment, there was a marked increase of GAP-43-stained cells in the whole olfactory region, which correlated with the observed regeneration at that time. Two weeks after dichlobenil treatment, the damaged atypical epithelium in the olfactory region showed a distinct keratin staining of basal and columnar cells whereas GAP-43-stained cells were not found. Despite a transient increase of GAP-43-stained cells in the border zone between damaged and undamaged olfactory mucosa, an expansion of a normal neuroepithelium into the damaged olfactory region was not detected in the dichlobenil-treated mice. An intact lamina propria is suggested as a prerequisite for repopulation of the neuroepithelium after toxicant-induced injury.