Rising of intracellular NAD+ level and oppositely directed changes in CD38 expression in hippocampal cells in experimental Alzheimer’s disease

The aim of the study was to assess the level of NAD⁺ in the brain of mice treated with beta-amyloid (Aβ), as well as to determine the activity of ADP-ribosyl cyclase/CD38 and the number of CD38-immunopositive neurons, astrocytes and endothelial cells. Material and methods. The Alzheimer’s disease model was reproduced by intrahippocampal administration of Aβ to C57BL/6 mice. Determination of the NAD⁺ level in the extracellular fluid of the brain and in the hippocampal tissue was carried out by spectrophotometric analysis. Evaluation of the enzymatic activity of ADP-ribosyl cyclase / CD38 was carried out by the fluorimetric method, determination of the number of CD38-immunopositive cells by the immunohistochemistry method. Results and discussion. The level of NAD⁺ was significantly increased in the hippocampal tissue in mice after administration of Aβ, while the level of extracellular NAD⁺ did not change. The activity of ADP-ribosyl cyclase / CD38 in the hippocampal tissue did not change, but the number of CD38-immunopositive neurons decreased, and the number of CD38⁺ endothelial cells increased in the hippocampus of mice after administration of Aβ. Conclusion. Opposite changes in the expression of ADP-ribosyl cyclase / CD38 in neurons and endotheliocytes correspond to different metabolic states of these types of cells and, along with an increased intracellular pool of NAD⁺ in experimental Alzheimer’s disease, reflect an adaptive stress response to Aβ administration.

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