Age-Related Changes of the Regeneration Mode in the Mouse Peripheral Olfactory System Following Olfactotoxic Drug Methimazole-Induced Damage
Age-Related Changes of the Regeneration Mode in the Mouse Peripheral Olfactory System Following Olfactotoxic Drug Methimazole-Induced Damage
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DOI：
10.1002/cne.22611
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发表时间：
2011-08-01
影响因子：
2.5
通讯作者：
Yamasoba, Tatsuya
中科院分区：
文献类型：
--
作者：
Suzukawa, Keigo;Kondo, Kenji;Yamasoba, Tatsuya
我们研究了小鼠外周嗅觉系统在嗅觉毒性药物诱导的损伤后再生模式的年龄相关变化。给出生后10天、3个月和16个月的小鼠腹腔注射甲巯咪唑，以造成嗅觉神经上皮的损伤。嗅神经上皮细胞收获和化学分析在不同的postlesion时间点，从1天到94天，调查神经上皮细胞增殖，神经元分化的时间过程中，神经上皮的重建，和神经支配的嗅球。使用香草醛回避行为测试评估功能恢复。Ki 67、β III微管蛋白和嗅觉标志物蛋白（神经元细胞增殖和分化的分子标志物）表达的时间模式在不同年龄组之间变化相似。与此相反，神经上皮细胞增殖损伤后的程度随着年龄的增长而下降，和嗅神经上皮和嗅球的神经支配的最终组织学恢复显着较小的16个月大的组相比，年轻的年龄组。这些结果表明，年龄相关的嗅觉神经上皮细胞重建神经上皮的能力下降与其年龄相关的神经上皮细胞损伤后，而不是在神经元分化的过程中的变化，增殖活性下降。尽管这些不完整的解剖恢复，16个月大的小鼠恢复的能力，以避免香草醛溶液的损伤后1个月，这表明解剖上皮损伤的程度不一定是成比例的嗅觉阈值。J. Comp.神经元519：2154-2174，2011。(C)2011 Wiley-Liss，Inc.
We investigated age-related changes in the mode of regeneration in the mouse peripheral olfactory system after olfactotoxic drug-induced damage. Mice at postnatal ages of 10 days, 3 months, and 16 months were given an intraperitoneal injection of methimazole to produce damage in the olfactory neuroepithelium. The olfactory neuroepithelia were harvested and analyzed immunohistochemically at various postlesion timepoints, from 1 day through to 94 days, to investigate neuroepithelial cell proliferation, the time course of neuronal differentiation, the reconstitution of neuroepithelium, and the innervation of the olfactory bulb. Functional recovery was assessed using the vanillin avoidance behavioral test. The chronological pattern in the expression of Ki67, beta III tubulin, and olfactory marker protein, molecular markers for neuronal cell proliferation and differentiation, changed similarly among the different age groups. In contrast, the extent of neuroepithelial cell proliferation after injury decreased with age, and the final histological recovery of the olfactory neuroepithelium and the innervation of the olfactory bulb were significantly smaller in the 16-month-old group compared to the younger age groups. These results suggest that the age-related decline in the capacity of olfactory neuroepithelium to reconstitute neuroepithelium is associated with its age-related decrease in proliferative activity after the neuroepithelial injury rather than changes in the process of neuronal differentiation. In spite of these incomplete anatomical recoveries, 16-month-old mice regained the ability to avoid vanillin solution by 1 month postlesion, suggesting that the extent of anatomical epithelial damage is not necessarily proportional to the threshold of olfactory perception. J. Comp. Neurol. 519: 2154-2174, 2011. (C) 2011 Wiley-Liss, Inc.