Acute Nicotinamide Adenine Dinucleotide Supplementation via Nicotinamide Mononucleotide Does Not Rescue Functional Impairment in a Lipopolysaccharide-induced Delirium Mouse Model.

Delirium is a serious neuropsychiatric condition that lacks an effective treatment intervention. A confusional state often brought on by acute illness, delirium is associated with acute inflammation and metabolic dysfunction. Nicotinamide adenine dinucleotide is a metabolite involved in both cellular energy generation and immunomodulation, that has previously been found to promote metabolic function and reduce inflammation. Whether Nicotinamide adenine dinucleotide supplementation may be beneficial for delirium has not been explored yet. In this study, we investigate the effect of acute supplementation of nicotinamide mononucleotide, a direct precursor of Nicotinamide adenine dinucleotide, in a lipopolysaccharide-induced delirium mouse model. While Nicotinamide adenine dinucleotide did not rescue the delirium-like sickness behavior and metabolic dysfunction in mice, a comprehensive cytokine profile analysis did reveal rescue of plasma IFNγ levels by nicotinamide mononucleotide supplementation and partial improvement on the levels of IL-12p40, RANTES, LIX, and IL-17 which were sex-dependent.