Olfactory Dysfunction in Diabetic Rats is Associated with miR-146a Overexpression and Inflammation

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.