Acute NAD+ Supplementation via NMN Does Not Rescue Functional Impairment in a LPS-Induced Delirium Mouse Model

Abstract

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. NAD+ is a metabolite involved in both cellular energy generation and immunomodulation, that has previously been found to promote metabolic function and reduce inflammation. Whether NAD+ supplementation may be beneficial for delirium has not been explored yet. In this study, we investigate the effect of acute supplementation of NMN, a direct precursor of NAD+, in a LPS-induced delirium mouse model. While NAD+ 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 NMN supplementation and partial improvement on the levels of IL-12p40, RANTES, LIX, and IL-17 which were sex dependent.