The effect of metformin treatment on BDNF gene expression and cognitive functions in prediabetic animal model

The prevalence of prediabetes is increasing rapidly in recent years. Prediabetes related factors such as macrovascular and microvascular complications, glucose toxicity, hyperinsulinemia have been suggested to be involved cognitive impairment in prediabetes, additionally risk factors that are linked to prediabetes; obesity can also cause cognitive impairments. In a recent human genome-wide association study, the role of the central nervous system in body mass regulation was strongly emphasized. In the present study, after prediabetes is induced by feeding wistar rats with high fat diets, the possible relationship between BDNF gene expression levels and learning-memory in the hippocampus which is the learning-related area in the brain will be investigated in the prediabetic animals. We assessed the importance of intact endogenous hypothalamic or hindbrain BDNF/TrkB signaling in the central regulation of energy balance with 32 Wistar rats respectively, comparing metabolic parameters and cognitive functions under high-fat diet or chow fed conditions. Our data show that when fed a high-fat diet, rats have significantly increased body weight and adiposity that is likely driven by reduced locomotor activity and core body temperature. In addition, under high fat diet conditions, rats show increased blood glucose levels and decreased cognitive functions (p=0.044). When Metformin administration rats show decreased blood glucose levels and increased cognitive functions (p=0.042). Taken together, our findings demonstrate that BDNF/TrkB is a novel metabolic and cognitive functions regulator and that enhanced signaling may contribute to the beneficial metabolic effects and cognitive functions.