Olfactory epithelia exhibit progressive functional and morphological defects in CF mice
Olfactory epithelia exhibit progressive functional and morphological defects in CF mice
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DOI：
10.1152/ajpcell.00106.2007
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发表时间：
2007-08-01
影响因子：
5.5
通讯作者：
Ostrowski, Lawrence E.
中科院分区：
文献类型：
--
作者：
Grubb, Barbara R.;Rogers, Troy D.;Ostrowski, Lawrence E.
在正常鼻上皮中，嗅受体神经元（orn）通过祖细胞的分化不断被替换。囊性纤维化（CF）小鼠的嗅上皮（OE）在出生时看起来正常，但到6个月大时，支撑细胞明显畸形，嗅觉受体神经元明显减少。嗅觉电图显示，30天龄CF小鼠的气味诱发反应减少了45%；在老年CF小鼠中，与野生型（WT）反应相比，观察到类似70%的减少。与CF气道上皮的研究一致，对CF小鼠分离的OE进行的室内研究显示，与WT小鼠相比，缺乏福斯克林刺激的Cl-分泌，并且酰胺敏感的钠吸收增加了12倍。我们推测，Na+的明显过度吸收，很可能是由嗅觉支撑细胞引起的，导致感觉纤毛所在的表层干燥，随后是嗅觉纤毛的变性。因此，CF小鼠提供了一种新的模型来研究疾病相关的嗅觉功能丧失的机制。
In normal nasal epithelium, the olfactory receptor neurons (ORNs) are continuously replaced through the differentiation of progenitor cells. The olfactory epithelium (OE) of the cystic fibrosis (CF) mouse appears normal at birth, yet by 6 mo of age, a marked dysmorphology of sustentacular cells and a dramatic reduction in olfactory receptor neurons are evident. Electroolfactograms revealed that the odor-evoked response in 30-day-old CF mice was reduced similar to 45%; in older CF mice, a similar to 70% reduction was observed compared with the wild type (WT) response. Consistent with studies of CF airway epithelia, Ussing chamber studies of OE isolated from CF mice showed a lack of forskolin-stimulated Cl- secretion and an similar to 12-fold increase in amiloride-sensitive sodium absorption compared with WT mice. We hypothesize that the marked hyperabsorption of Na+, most likely by olfactory sustentacular cells, leads to desiccation of the surface layer in which the sensory cilia reside, followed by degeneration of the ORNs. The CF mouse thus provides a novel model to examine the mechanisms of disease-associated loss of olfactory function.