Nicotinamide adenine dinucleotide concentrations in a mouse model of Down Syndrome

Abstract

Individuals with Down Syndrome (DS) may experience impaired cardiac and skeletal muscle function, resulting in lower work and exercise capacity, lower blood pressure, and reduced cardiovascular responses.Nicotinamide adenine dinucleotide (NAD) is critical for maintaining mitochondrial function. It transfers electrons within cells, acting as a messenger between metabolism and cell signals. It is uncertain whether DS pathophysiology is caused by an imbalance of NAD and/or changes in mitochondrial activity. Our study analyzed the levels of NAD in the tissue of wild-type and Ts65Dn (a mouse model of DS) mice. We hypothesized that NAD levels are differentially regulated in WT and Ts65Dn mouse tissue.NAD concentration was analyzed using a kinematic fluorescence assay. We normalized NAD concentration based on the tissue mass of each aliquot and corrected for between-plate differences using internal control samples. We found significantly different NAD concentrations in the left ventricle of Ts65Dn mice (WT, 22.8±5.1 mmol/mg, TS65 Dn, 15.3±4.1 mmol/mg [mean±SD], p=0.003), and non-significant but reduced concentrations in skeletal muscle (quadriceps, tibialis anterior), and kidney tissues of Ts65Dn animals. Our findings suggest that, based on our findings in a mouse model of DS, reduced NAD levels may be a part of the pathophysiology associated with DS. Characterizing this phenotype could lead to a better understanding of potential drug targets to alleviate the impaired cardiac and skeletal muscle function of DS, allowing for improved work and exercise capacity. This work was supported by a Gettysburg College Professional Development Grant to JB. LD was supported by NIH grants 1R15 HD076379, 3R15 HD076379-S1, 3R15 HD076379-S2, and 1R21HD099573. Further funding was provided by the Cross-disciplinary science institute at Gettysburg College via the Dickson Fund; Kolbe Fund; Albaugh Fund in Chemistry; Alberte Fund in Biology; and the Cormack, Hendrickson, Peterson and Schweizer Funds in Physics. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.