Analysis of the Relationship Between Learning and Synaptophysin in Obese Rats Treated With DPP4 Inhibitor

Abstract

In this study, it is aimed to investigate possible changes in cognitive functions in obesity by using targeted treatment hypothesis. Accordingly, the effects of DPP4 inhibitor, which is actively used in the clinic in the treatment of diabetes, and the effect of exercise, which has been proven to be effective in the treatment of obesity, on the change of learning performance and the relationship of these effects with the synaptophysin molecule were investigated. In our study, 42 Wistar albino rats were used. The animals were randomly divided into seven groups as obese, control, obese+DPP4i, control+DPP4i, obese+exercise, control+exercise, control+NaCl. To create experimental obesity, the animals that are targeted to be obese were separated and fed on a high fat diet for 8 weeks. After the obese model was created, sitagliptin was applied to the DPP4i groups and swimming exercise was applied to the exercise groups for obesity treatment. The last week of the study was performed reference memory learning test to the whole group with Morris water maze. Then, the hippocampus tissues were removed from the animals under anesthesia. mRNA and protein isolations were performed from the extracted tissues. Synaptophysin gene expressions were determined from mRNA samples by Real-Time PCR method. Synaptophysin protein levels were determined from protein lysates by Western Blot method. In the learning test, in the obese groups, there was a statistically significant difference between the average escape time of the DPP4i and exercise groups and the groups that did not (p<0.05). As a result, in groups where obesity is treated with DPP4i and exercise; It was concluded that cognitive performance was better than obese groups. There was a evident decrease in synaptophysin gene expression levels in obese groups compared to the control group. In the treatment groups, an increase was observed in synaptophysin gene expression levels in the DPP4 inhibitor and especially in the exercise groups compared to the control groups (P> 0.05). Gene expression results were similar in analyzes performed at the protein level. According to these results, in terms of performance in cognitive function due to obesity and synaptophysin gene relationship; DPP4 inhibitor showed as effective a result as exercise. This provides a resource for advanced molecular and metabolic research.Acknowledgement: This study was supported by The Scientific And Technological Research Council Of Turkey (TÜBİTAK) Project No. 219S063.