NAD+ affects differentially expressed genes-MBOAT2-SLC25A21-SOX6 in experimental autoimmune encephalomyelitis model.

ABSTRACT

BACKGROUND: Nicotinamide adenine dinucleotide (NAD+) plays a key role in neuroinflammation and neurodegeneration and provides anti-inflammatory and neuroprotective effects in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). AIM: In this study, we aimed to investigate whether NAD+ affects differentially expressed genes (DEGs) in splenocytes of EAE mice to reveal candidate genes for the pathogenesis of MS. METHODS: The EAE model was used to perform an intervention on NAD+ to investigate its potential as a protective agent in inflammation and demyelination. Transcriptome analysis of nerve tissue was carried out to gain better insights into NAD+ function. Effects of NAD+ on DEGs in the splenocytes of EAE mice were investigated to determine its anti-inflammatory effect. RESULTS: NAD+ in EAE mice showed the clinical score was significantly improved (EAE 3.190 ± 0.473 vs. NAD+ 2.049 ± 0.715). DEGs (MBOAT2, SLC25A21, and SOX6) between the EAE and the EAE + NAD+ groups showed that SOX6 was significantly improved after NAD+ treatment compared with the EAE group, and other indicators were improved but did not reach statistical significance. NAD+ exhibited clinical scores in EAE mice, and key inflammation was ameliorated in EAE mice spleen after NAD+ intervention, while transcriptome analysis between EAE and EAE + NAD+ groups showed several DEGs in the underlying mechanism. CONCLUSION: NAD+ on DEGs attenuates disease severity in EAE. Transcriptome analysis on nerve tissue reveals several protein targets in the underlying mechanisms. However, NAD+ does not significantly improve DEGs in the splenocytes of the EAE model.

MBOAT2, SLC25A21, and SOX6 show significant fold change in EAE mice, while SOX6 shows significantly lower expression in the EAE group and the EAE + NAD+ group compared with the Ctrl.NAD+ in the EAE model provides its protective role in inflammation and demyelination.NAD+ exhibits clinical scores in EAE mice.NAD+ does not significantly improve DEGs in splenocytes of the EAE.