Investigation of CYCLO-Z therapeutic effect on insulin pathway changes observed in alzheimer's model by biochemical and electrophysiological parameters

Objective: In our study, it was aimed to investigate the molecular mechanisms of the insulin pathway, changes in memory and brain oscillations in the early period AD rat model created by AβO injection. In addition, it is aimed to reveal the effect of the Cyclo-Z therapeutic agent on these changes. Method: SH, SHZ, AH and AHZ groups were formed, including 20 male Wistar rats 3 months old in each group. Cyclo-Z agent containing 10 mg Zn / kg and 0,2 mg SHP / kg was administered to SHZ and AHZ groups for 3 weeks following the recovery period. Equal volumes of tap water were applied to the SH and AH groups with the Cyclo-Z applied groups. At the end of this process, object and position memory tests were performed and spontaneous EEG records were taken to determine AβO-induced brain activity changes. At the end of the experimental process, biochemical analyzes were performed in the hippocampus and total brain tissues of the rats. It has been observed that AH pathology causes a decrease in delta power values of sleep EEG. Results: While Cyclo-Z treatment had a positive effect on weight loss, peripheral insulin resistance and brain insulin amounts in the AHZ group, it had an adverse effect on the SHZ group due to Zn+2 toxicity. AβO toxicity was decreased in AHZ group rats due to the increase in IDE and NEP enzymes, but Tau Ser356 caused an increase in phosphorylation. Although the levels of IDE and NEP enzymes were increased in the SHZ group, it was observed that AβO accumulation and tau toxicity increased due to Zn+2 toxicity. The cyclo-Z agent enhanced the object and localization memory tests of the SHZ and AHZ groups. Cyclo-Z treatment was found to have a significant effect on increasing spindle power values, especially in the left temporal region. Conclusion: Our findings show that Cyclo-Z agent has significant therapeutic effects on molecular changes, memory and brain oscillations that occur in the early stages of AD disease. Key words: Amyloid-beta oligomer, insulin, Cyclo-Z, memory, EEG