Conclusions
NAD+ exerted a protective effect on EAE mice by inhibiting PI3K/Akt/mTOR signaling pathway through SIRT1 in TECs, and prevented EAE mice from sustained damage.
Methods
Bioinformatic analysis was used to identify hub genes. Forty female C57BL/6 mice were randomly divided into 4 groups: control, EAE, NAD+, and NAD+ +SIRT1 inhibitor (SIRT-IN-3) groups and SIRT1 group. The NAD+ group and SIRT1 inhibitor group were treated with NAD+ drug and fed for 4 weeks. The neurological function scores were evaluated weekly. The thymus tissues of wild-type mice were removed, ground and filtered into single-cell suspension. MOG 35-55 (1 μg/mL) was given to primary thymic epithelial cells (TECs) to induce EAE model in vitro. The expression of LC-3A/B was observed by immunofluorescence. The expressions or the activation/phosphorylation of associated proteins were detected by Western blot.
Objective
To investigate the effect of NAD+ on thymus autophagy in experimental autoimmune encephalomyelitis (EAE) mice through SIRT1.
Results
Enrichment analysis showed PI3K-Akt-mTOR and autophagy pathway were main terms in EAE diseases, and the relationship between NAD+ and SIRT1. The activation of p-PI3K, p-Akt and p-mTOR were the highest in the EAE group consistent with decreased P62, Beclin1, LC-3A/B and SIRT1, and NAD+ reversed these results, furthermore SIRT1 inhibitor: SIRT-IN3 weakened the NAD+' effects in both in vivo and in vitro experiments. Immunofluorescence study in vivo and in vitro were accord with the results of western blot. Conclusions: NAD+ exerted a protective effect on EAE mice by inhibiting PI3K/Akt/mTOR signaling pathway through SIRT1 in TECs, and prevented EAE mice from sustained damage.