Immunohistochemical analysis of Klotho protein expression in the brain of aging rats with diabetes mellitus under pharmacological correction

The Klotho protein is one of the key regulators of aging and metabolism in the brain of aging rats. The relevance of the work is due to the high prevalence of diabetic encephalopathy in elderly people with diabetes and the lack of knowledge of the mechanisms of its correction. Materials and methods. Type 1 diabetes was modeled on 36 Wistar rats at the age of 12 months by administration of streptozotocin. After 6 months of hyperglycemia, the animals received aminalon (1000 mg/kg/day) or succicard (50 mg/kg /day) for 30 days. The expression of Klotho protein in the retrosplenic cortex, hippocampus, thalamus, and hypothalamus was evaluated by immunohistochemistry. Quantitative analysis was performed using the ImageJ program, statistical significance was determined using ANOVA. Results and discussion. In rats with DM without treatment, lower levels of IRM expression using polyclonal antibodies against the Klotho protein were detected in the retrosplenic cortex, hippocampus, thalamus and hypothalamus, which, in comparison with intact animals, indicates a possible dysfunction of neuronal metabolism and a decrease in the protective activity of the Klotho protein in conditions of diabetic neurodegeneration. During aminalon therapy, the expression level of Klotho was higher than in animals without therapy. During Succicard therapy, Klotho levels exceeded those of the untreated group, but were inferior to aminalon. Conclusions. When modeling diabetes mellitus (DM), a decrease in the expression of immunoreactive material was noted when using antibodies against the Klotho protein in the retrosplenic cortex, hippocampus, thalamus and hypothalamus of rats, which indicates the appearance of signs of premature aging in brain structures against the background of triggering neuroinflammation processes, which contributes to the development of diabetic enephalopathy. During aminalon therapy, the expression level of the Klotho protein increased significantly. Treatment with succicard diabetes contributed to a less pronounced increase in the level of Klotho protein expression compared with aminalon. The results of the study confirm the prospects of searching for a number of GABA derivatives in diabetes, taking into account metabolic disorders in the Klotho/FGF 23 signaling pathway (fibroblast growth factor 23, fibroblast growth factor 23) in key cerebral structures.