Type 2 diabetes (T2D) is associated with cognitive decline and dementia. Both neurodegenerative conditions are characterized by olfactory dysfunction (OD) which is also observed in diabetic patients. Diabetes and neurodegeneration display altered miRNAs expression; therefore, the study of miRNAs in the diabetic olfactory system is important in order to know the mechanisms involved in neurodegeneration induced by T2D. In this work we evaluated the expression of miRs206, 451, 146a and 34a in the olfactory bulb (OB) of T2D rats and its association with OD. T2D induction was performed by administering streptozotocin to neonatal rats. The olfactory function was evaluated after reaching the adulthood by employing the buried pellet and social recognition tests. After 18 weeks, animals were sacrificed to determinate miRNAs and protein expression in the OB. T2D animals showed a significant increase in the latency to find the odor stimulus in the buried pellet test and a significant reduction in the interest to investigate the novel juvenile subjects in the social recognition test, indicating OD. In miRNAs analysis we observed a significant increase of miR-146a expression in the OB of T2D rats when compared to controls. This increase in miR-146a correlated with the overexpression of IL-1β in the OB of T2D rats. The present results showed that OD in T2D rats is associated with IL-1β mediated-inflammation and miR-146a overexpression, suggesting that high levels of IL-1β could trigger miR-146a upregulation as a negative feedback of the inflammatory response in the OB of T2D rats.

中文翻译：

---

糖尿病大鼠的嗅觉功能障碍与miR-146a过表达和炎症相关。

2型糖尿病（T2D）与认知能力下降和痴呆症相关。两种神经退行性疾病的特征都是嗅觉功能障碍（OD），这在糖尿病患者中也观察到。糖尿病和神经退行性变表现出改变的miRNA表达。因此，研究糖尿病嗅觉系统中的miRNA对于了解T2D诱导的神经变性所涉及的机制非常重要。在这项工作中，我们评估了miRs206、451、146a和34a在T2D大鼠嗅球（OB）中的表达及其与OD的关系。通过给新生大鼠施用链脲佐菌素来进行T2D诱导。成年后，通过使用掩埋的小球和社会认可测试评估嗅觉功能。18周后，处死动物以确定OB中的miRNA和蛋白质表达。T2D动物在掩埋颗粒试验中发现气味刺激的潜伏期显着增加，而在社交识别试验中研究新型少年受试者的兴趣显着降低，表明为OD。在miRNA分析中，我们观察到与对照组相比，T2D大鼠OB中miR-146a表达显着增加。miR-146a的这种增加与T2D大鼠OB中IL-1β的过表达有关。目前的结果表明，T2D大鼠中的OD与IL-1β介导的炎症和miR-146a过表达有关，提示高水平的IL-1β可能触发miR-146a上调，作为OB炎症反应的负反馈。 T2D大鼠。