Fukuda Yuriko, Katsunuma Sayaka, Uranagase Atsuhiro, Nota Jumpei, Nibu Ken-Ichi
Kobe University Graduate School of Medicine.
Kobe Red Cross Hospital.
Neuroreport. 2018 Nov 7;29(16):1400-1404. doi: 10.1097/WNR.0000000000001125.
In the mammalian olfactory epithelium (OE), neurogenesis continues throughout the lifetime, by replacing olfactory receptor neurons (ORNs) lost by normal turnover in the postnatal period. However, this ability decreases with age and/or because of various toxic factors. To date, no effective treatment for olfactory dysfunction' especially because of aging, is available in clinical practice. Here, we examined the effects of intranasal administration of fibroblast growth factor-2 and insulin-like growth factor-1 in gelatin hydrogel on the degenerated OE of aging mice induced by methimazole administration. These topical treatments led to increases in the number of olfactory marker protein-positive cells, which identified mature ORNs, resulting in the increased thickness of OE. These results indicate that both fibroblast growth factor-2 and insulin-like growth factor-1 promote the proliferation of basal cells and differentiation of immature ORNs into mature ORNs in the degenerated OE of aging mice. These agents might be promising candidates for the treatment of degenerated OE of aging humans.
在哺乳动物的嗅觉上皮（OE）中，神经发生在整个生命周期中持续进行，通过替换出生后正常更新过程中丢失的嗅觉受体神经元（ORN）。然而，这种能力会随着年龄增长和/或由于各种毒性因素而下降。迄今为止，在临床实践中尚无针对嗅觉功能障碍（尤其是由于衰老导致的）的有效治疗方法。在此，我们研究了在明胶水凝胶中鼻内给予成纤维细胞生长因子-2和胰岛素样生长因子-1对由给予甲巯咪唑诱导的衰老小鼠退化的OE的影响。这些局部治疗导致嗅觉标记蛋白阳性细胞数量增加，这些细胞可识别成熟的ORN，从而使OE厚度增加。这些结果表明，成纤维细胞生长因子-2和胰岛素样生长因子-1均可促进衰老小鼠退化的OE中基底细胞的增殖以及未成熟ORN向成熟ORN的分化。这些药物可能是治疗衰老人类退化OE的有前景的候选药物。
