Regression analysis of mitochondrial proapoptotic molecules, oxidative stress, and cellular respiration parameters in the hippocampus of rats with experimental Alzheimer’s disease

BACKGROUND. Apoptosis is a key mechanism contributing to the loss of neurons and glial cells in Alzheimer’s disease (AD). AIM. To establish the relationship between the concentrations of mitochondrial proapoptotic molecules, oxidative stress, and cellular respiration parameters in the hippocampal tissue of rats with experimental Alzheimer’s disease. MATERIALS AND METHODS. The study was conducted on male and female Wistar rats in which Alzheimer’s disease was experimentally induced by direct injection of amyloid beta-peptides (Aβ) aggregates into the CA1 region of the hippocampus. Sixty days post-injection, the concentrations of proapoptotic mitochondrial molecules — SMAC/DIABLO protein, apoptosis-inducing factor (AIF), and cytochrome c — were measured in hippocampal tissue. These concentrations were analyzed in relation to mitochondrial hydrogen peroxide levels and the activities of aerobic and anaerobic cellular respiration. Regression models were characterized using the F-test, Akaike information criterion (AIC), and the coefficient of determination (R2). RESULTS. A significant increase (p < 0.05) in the concentrations of proapoptotic molecules was observed in the hippocampal tissue of both male and female rats following Aβ injection. Regression analysis revealed that the release of SMAC/DIABLO protein and apoptosis-inducing factor was most strongly associated with mitochondrial hydrogen peroxide levels, whereas the release of cytochrome c was primarily dependent on anaerobic respiration activity. CONCLUSION. In both male and female rats with experimental Alzheimer’s disease, the increased concentrations of SMAC/DIABLO protein and apoptosis-inducing factor in hippocampal tissue are associated with elevated mitochondrial hydrogen peroxide levels. The increased concentration of cytochrome c is primarily linked to enhanced anaerobic respiration activity.