Dose-Dependent Effects of Insulin-Like Growth Factor 1 in the Aged Olfactory Epithelium
Dose-Dependent Effects of Insulin-Like Growth Factor 1 in the Aged Olfactory Epithelium
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DOI：
10.3389/fnagi.2018.00385
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发表时间：
2018-11
影响因子：
4.8
通讯作者：
R. Ueha;K. Kondo;S. Ueha;T. Yamasoba
中科院分区：
文献类型：
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作者：
R. Ueha;K. Kondo;S. Ueha;T. Yamasoba
背景：嗅觉被认为是随着年龄的增长而受损的。我们假设，适当剂量的胰岛素样生长因子-1（IGF-1）可以预防年龄诱导的嗅觉受体神经元（ORN）的负面影响。我们探讨了低剂量和高剂量IGF-1给药对老年小鼠ORN细胞系统的影响，并研究了IGF-1参与老年小鼠ORN再生的细胞机制。研究方法：我们皮下注射重组人胰岛素样生长因子-1（rhIGF-1）的16个月大的雄性小鼠超过56天，然后检查rhGF-1的细胞组成，细胞增殖和细胞死亡的老年嗅上皮（OE）的组织学影响，通过比较生理盐水处理和低，高剂量rhIGF-1处理的小鼠。结果如下：低剂量rhIGF-1给药增加了OE中嗅觉祖细胞、未成熟ORN和成熟ORN的数量，尽管Cas 3+凋亡细胞增加。值得注意的是，高剂量rhIGF-1给药仅增加了未成熟ORN的数量，而不是嗅觉祖细胞和成熟ORN的数量，同时增加了凋亡细胞。结论：我们的数据表明，在老年小鼠中，以适当剂量给予IGF-1可以增加成熟ORN的数量，进一步的人体研究可能有助于开发衰老相关嗅觉障碍的治疗方法。
Background: Olfaction is known to be impaired by aging. We hypothesized that insulin-like growth factor-1 (IGF-1) administered at an appropriate dose could prevent age-induced negative effects on olfactory receptor neurons (ORNs). We explored the effects of low- and high-dose administration of IGF-1 on the ORN cell system in aged mice and investigated the involvement of the cellular mechanisms of IGF-1 in the regeneration of ORNs in aged mice. Methods: We subcutaneously administered recombinant human IGF-1 (rhIGF-1) to 16-month-old male mice over 56 days, and then examined the histological effects of rhGF-1 on cellular composition, cell proliferation, and cell death in the aged olfactory epithelium (OE), by comparing among saline-treated and low- and high-dose rhIGF-1-treated mice. Results: Low-dose rhIGF-1 administration increased the numbers of olfactory progenitors, immature ORNs, and mature ORNs in the OE, despite an increase in Cas3+ apoptotic cells. Notably, high-dose rhIGF-1 administration increased the numbers of only immature ORNs, not olfactory progenitors and mature ORNs, with a concurrent increase in apoptotic cells. Conclusion: Our data suggest that in aged mice, IGF-1 administered at an appropriate dose could increase the number of mature ORNs and further human studies may contribute to the development of treatments for aging-related olfactory impairment.