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

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.