Investigation of the protective effects of vortioxetine and Crocin 1 in the corticosterone-induced rat depression model

In clinical and experimental animal studies on depression, many differences can be observed in both the treatment and pathophysiology of depression. The region with the highest concentration of receptors related to stress hormones is the hippocampus area of the brain. Therefore, in our study in which we created experimental stress and depression with corticosteroids in rats, we aimed to protect neural functions, especially in the hippocampal region, with the application of Crocin I sevartioxetine, and to measure and identify new targets in the development of antidepressant treatment by measuring the parameters that can be used for this purpose, and by evaluating them. In the study, 28 Sprague-Dawley rats about weight of 200-220 g have been used. The rats were seperated to 4 groups, each of which has 7 rats. Group1; control group (6 weeks), Group2; Corticosterone (6 weeks), Group3; After corticosterone administration, 20 mg/kg oral Crocin I was started on the 15th day and administered at the end of the 6th week.. Group 4: After corticosterone administration, 10 mg/kg Vortioxetine was started on the 15th day and administered until the end of the 6th week. Rats were decapited after the study. After the serum part was separated, it was put into separate tubes for biochemistry and ELISA studies. After the completion of the 6th week of the experimental period, the rats were decapitated and blood and brain tissue were collected. The blood sample taken from the rats was centrifuged at 4000 rpm for 15 minutes after waiting for 30 minutes. Samples were stored at -20 ℃ for biochemical analysis and at -80 ℃ for ELISA studies. When Agmatine, LPS and NGF levels were measured in the depressed group, a statistically significant decrease was observed compared to the control group, while a significant increase was detected in the treatment groups. When BDNF levels were measured in the depressed group, a significant increase was observed compared to the control group, while a significant increase was observed in the corticosterone + crocin 1 group, one of the treatment groups. When glucose, cholesterol, triglyceride, HDL and LDL levels were measured in the depressed group, a statistically significant increase was observed compared to the control group, while a significant decrease was detected in the Corticosterone + Vortioxetine treatment group. When IL-6, IL-10, TNF-α levels were measured, a statistically significant increase was observed, while a significant decrease was detected in the treatment groups. A statistically significant increase in CD68 immunoreactivity was detected in the Corticosterone group compared to the control group (p = 0.001). A statistically significant decrease was detected in the Corticosterone + Crocin-1 (p = 0.007) and Corticosterone + Vortioxetine (p = 0.008) groups when compared to the Corticosterone group. However, no difference was observed between the Corticosterone + Crocin-1 and Corticosterone + Vortioxetine groups (p = 0.987). In biochemical analyses, serum glucose, cholesterol, AST, ALT, VLDL, LDL, HDL, insulin and C-peptide levels were measured on an autoanalyzer. IL-6, IL-10, 1L-1Beta, NGF, BDNF, Tumor necrosis factor (TNF-α) and C reactive protein (CRP) levels were measured with ELISA kit. Agmatine and biogenic amine levels were measured by HPLC. Again, in order to evaluate metabolic endotoxemia, lipopolysaccharide levels in the serum of rats were studied with a commercial ELISA kit. CD68 was detected in brain tissue by immunohistochemistry. In our study, there was a significant decrease in agmatine levels, which is thought to play a role in the clinical picture with neurological damage and emotional symptoms in stress and depression, in the corticosterone group compared to the control group. Although agmatine levels in the Crocin 1 applied group increased significantly and were close to the control group values, agmatine levels in the vortioxetine group were lower than corticosterone levels. It was observed that it was similar to the group. This was particularly significant as it showed that Crocin 1 application was more beneficial than the synthetic drug vortioxetine.