Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Toxicol Sci. 2011 Mar;120(1):163-72. doi: 10.1093/toxsci/kfq387. Epub 2010 Dec 20.
Manganese (Mn) is an essential nutrient with potential neurotoxic effects. Mn deposited in the nose is apparently transported to the brain through anterograde axonal transport, bypassing the blood-brain barrier. However, the role of the olfactory epithelial cells in Mn transport from the nasal cavity to the blood and brain is not well understood. We utilized the methyl bromide (MeBr) lesion model wherein the olfactory epithelium fully regenerates in a time-dependent and cell type-specific manner over the course of 6-8 weeks postinjury. We instilled (54)MnCl(2) intranasally at different recovery periods to study the role of specific olfactory epithelial cell types in Mn transport. (54)MnCl(2) was instilled at 2, 4, 7, 21, and 56 days post-MeBr treatment. (54)Mn concentrations in the blood were measured over the first 4-h period and in the brain and other tissues at 7 days postinstillation. Age-matched control rats were similarly studied at 2 and 56 days. Blood and tissue (54)Mn levels were reduced initially but returned to control values by day 7 post-MeBr exposure, coinciding with the reestablishment of sustentacular cells. Brain (54)Mn levels also decreased but returned to control levels only by 21 days, the period near the completion of neuronal regeneration/bulbar reinnervation. Our data show that Mn transport to the blood and brain temporally correlated with olfactory epithelial regeneration post-MeBr injury. We conclude that (1) sustentacular cells are necessary for Mn transport to the blood and (2) intact axonal projections are required for Mn transport from the nasal cavity to the olfactory bulb and brain.
锰(Mn)是一种必需的营养物质,具有潜在的神经毒性作用。沉积在鼻子中的 Mn 显然通过顺行轴突运输被转运到大脑,绕过血脑屏障。然而,嗅上皮细胞在 Mn 从鼻腔向血液和大脑的转运中的作用尚不清楚。我们利用甲基溴(MeBr)损伤模型,其中嗅上皮细胞在损伤后 6-8 周内以时间依赖性和细胞类型特异性的方式完全再生。我们在不同的恢复时期经鼻腔内滴注(54)MnCl2 以研究特定嗅上皮细胞类型在 Mn 转运中的作用。(54)MnCl2 在 MeBr 处理后 2、4、7、21 和 56 天分别滴注。在滴注后第 7 天测量血液中(54)Mn 浓度,在第 7 天测量大脑和其他组织中的(54)Mn 浓度。在 2 和 56 天,年龄匹配的对照大鼠也进行了类似的研究。血液和组织中的(54)Mn 水平最初降低,但在 MeBr 暴露后第 7 天恢复到对照值,这与支持细胞的重建相吻合。大脑中的(54)Mn 水平也降低,但仅在 21 天恢复到对照水平,这是神经元再生/延髓再支配接近完成的时期。我们的数据表明,Mn 向血液和大脑的转运与 MeBr 损伤后嗅上皮细胞的再生在时间上相关。我们得出结论,(1)支持细胞是 Mn 向血液转运所必需的,(2)完整的轴突投射是 Mn 从鼻腔向嗅球和大脑转运所必需的。