Demianchuk O. Influence of alpha-ketoglutarate on Drosophila and mice: parameters of behavior, oxidative stress and energy metabolism

Object of study - biochemical processes in fruit flies D. melanogaster and laboratory mice M. musculus. The object of study - biochemical processes in fruit flies D. melanogaster and laboratory mice M. musculus. The study examined the effect of exogenous AKG on the physiological and biochemical parameters of the long-lived subline of Drosophila melanogaster (Canton S) and C57BL/6J mice. In Drosophila, the effect of AKG (10 mM) on life expectancy, motor activity, stress resistance, antioxidant status and energy processes was studied. In mice, the effects of AKG (1% in water) on open-field behavior and brain biochemical parameters on standard and high-calorie diets were evaluated. The analysis included levels of peroxides, glutathione, antioxidant enzyme activity, energy metabolites, and gene expression related to antioxidant response and autophagy. The study found that exogenous AKG does not affect the lifespan of Drosophila melanogaster on standard medium (5% sucrose, 5% yeast), but prolongs it on media with low protein and high sucrose content (9% sucrose, 1% yeast). AKG reduced the activity of antioxidant enzymes (catalase and glutathione S-transferase) and triacylglycerols, without changing the level of oxidative stress, energy metabolites, glycolysis enzymes and mitochondrial electron transport chain function. The addition of AKG affected the transcriptional activity of only certain genes associated with the Nrf2 signaling pathway. In C57BL/6J mice, AKG (1% in drinking water) caused anxiety behavior, as evidenced by a decrease in exploratory activity in the open field test both on the baseline and high-calorie diet. In the cerebral cortex of mice, AKG reduced the activity of antioxidant enzymes, but did not significantly affect the level of oxidative stress markers, glucose, mitochondrial function, and energy metabolism. The combination of AKG with cafeteria diet increased anxiety behavior and decreased antioxidant defense, but at the same time induced the expression of genes related to autophagy and FOXO signaling pathway. AKG may modulate oxidative stress and autophagy through the activation of its dependent enzymes, but the observed anxiety behavior emphasizes the need for further research.