Olfactory dysfunction significantly impedes the life quality of patients. Neuropeptide Y (NPY) is not only a neurotrophic factor in the rodent olfactory system but also an orexigenic peptide that regulates feeding behavior. NPY increases the olfactory receptor neurons (ORNs) responsivity during starvation; however, whether NPY can promote differentiation of human ORNs remains unexplored. This study investigates the effect of NPY on the differentiation of human olfactory neuroepithelial cells in vitro. Human olfactory neuroepithelium explants were cultured on tissue culture polystyrene dishes for 21 days. Then, cells were cultured with or without NPY at the concentration of 0.5 ng/mℓ for 7 days. The effects of treatment were assessed by phase contrast microscopy, immunocytochemistry and western blot analysis. The further mechanism was evaluated with NPY Y1 receptor-selected antagonist BIBP3226. NPY-treated olfactory neuroepithelial cells exhibited thin bipolar shape, low circularity, low spread area, and long processes. The expression levels of Ascl1, βIII tubulin, GAP43 and OMP were significantly higher in NPY-treated cells than in controls (p < 0.05). NPY-treated olfactory neuroepithelial cells expressed more components of signal transduction apparatuses, Golf and ADCY3, than those without NPY treatment. Western blot analysis also further confirmed these findings (p < 0.05). Additionally, the expression levels of Ascl1, βIII2 tubulin, GAP43, OMP, ADCY3, and Golf in BIBP3226 + NPY and controls were comparable (p > 0.05). NPY not only increases expressions of protein markers of human olfactory neuronal progenitor cells, but also promotes differentiation of ORN and enhances formation of components of olfactory-specific signal transduction pathway through Y1 receptors.

中文翻译：

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神经肽 Y 通过 Y1 受体增加人类嗅觉受体神经元的分化

嗅觉功能障碍严重影响患者的生活质量。神经肽 Y (NPY) 不仅是啮齿动物嗅觉系统中的神经营养因子，而且还是调节摄食行为的促食欲肽。NPY 在饥饿期间增加嗅觉受体神经元 (ORN) 的反应性；然而，NPY 是否可以促进人类 ORN 的分化仍有待探索。本研究探讨了 NPY 对体外人嗅神经上皮细胞分化的影响。人类嗅觉神经上皮外植体在组织培养聚苯乙烯培养皿上培养 21 天。然后，在含有或不含 NPY 浓度为 0.5 ng/mℓ 的情况下培养细胞 7 天。通过相差显微镜、免疫细胞化学和蛋白质印迹分析评估治疗效果。使用 NPY Y1 受体选择的拮抗剂 BIBP3226 评估了进一步的机制。NPY 处理的嗅觉神经上皮细胞表现出薄的双极形状、低圆形、低扩散区域和长突起。NPY 处理的细胞中 Ascl1、βIII 微管蛋白、GAP43 和 OMP 的表达水平显着高于对照（p < 0.05）。NPY 处理的嗅觉神经上皮细胞表达的信号转导装置 Golf 和 A​​DCY3 的成分比未经 NPY 处理的细胞更多。蛋白质印迹分析也进一步证实了这些发现（p < 0.05）。此外，BIBP3226 + NPY 和对照中 Ascl1、βIII2 微管蛋白、GAP43、OMP、ADCY3 和 Golf 的表达水平相当（p > 0.05）。NPY 不仅增加了人类嗅觉神经元祖细胞的蛋白质标志物的表达，