Pozdnyakov D. I. Mitochondrial cascade in the sporadic form of Alzheimer’s disease in an experiment. Laboratory Animals for Science. 2022; 2. https://doi.org/10.29296/2618723X-2022-02-06
Pathophysiological reactions of the «mitotondrial cascade» are an important component of the pathogenesis of neurodegenerative diseases, in particular Alzheimer’s disease, and can serve as a basis for neuroprotective intervention, which suggests the relevance of their study.
The aim of the study. To evaluate the dependence of changes in mitochondrial function parameters on changes in tau protein content in the hippocampus of rats in experimental Alzheimer’s disease of sporadic type.
Material and methods. Alzheimer’s disease was modeled in Wistar rats by injection of Aβ1–42 fragments into the CA1 part of the hippocampus. After 60 days of exposure, the development of cognitive deficits in rats was assessed in the Y-shaped maze test. Cognitive deficits in animals were assessed by changes in the number of spontaneous alternations of maze arms Changes of the ATP concentration, tau protein, mitochondrial hydrogen peroxide and the activity of enzymes: aconitase, citrate synthase, cytochrome c oxidase, succinate dehydrogenase were evaluated in the hippocampus of animals. The change in the value of the mitochondrial membrane potential was also evaluated. The content of ATP and tau protein was determined by enzyme immunoassay. The activity of mitochondrial enzymes was evaluated spectrometrically when the corresponding substrates were introduced into the reaction medium. The concentration of mitochondrial hydrogen peroxide was determined by a change in the fluorescence of resorufin. The membrane potential of mitochondria was evaluated by spectrophotometric method. The data was processed statistically. During the analysis, the Spearman correlation coefficient was calculated.
Results. The study found that in rats with Alzheimer’s disease, compared with sham-operated animals, there was a decrease in the activity of citrate synthase, aconitase, cytochrome c oxidase, succinate dehydrogenase, mitochondrial membrane potential and ATP concentration with an increase in the content of mitochondrial hydrogen peroxide and tau protein. Also, in rats with experimental pathology, the development of a pronounced cognitive deficit was observed, which directly correlated with a change in the concentration of tau protein (r=0.9950). In turn, changes of tau protein content correlated with changes of citrate synthase activity (r=0.95806) and ATP concentration (r=0.9798). The obtained data may indicate that the accumulation of phosphorylated tau protein aggregates in brain tissue in Alzheimer’s disease may depend from mitochondrial biogenesis (citrate synthase activity) and the integral activity of the cell mitochondria (ATP concentration).
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