Nicotinamide, a vitamin B3 ameliorates depressive behaviors independent of SIRT1 activity in mice

Zhuxi Liu, Caiqin Li, Xuelian Fan, Yifang Kuang, Xu Zhang, Lei Chen, Jinjing Song, Ying Zhou, Eiki Takahashi, Guang He, Weidong Li

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Sirtuin 1 (SIRT1), is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase and a candidate gene for depression. Nicotinamide (NAM), a form of vitamin B3, is reported as a potential inhibitor of SIRT1. Our previous study found that the 24-h-restraint stress could induce long-term depressive-like phenotypes in mice. These mice displayed increased SIRT1 activity. Here, we studied whether NAM was capable of attenuating depressive behaviors through inhibiting SIRT1 activity. Surprisingly, the application of NAM significantly reversed the depressive behaviors but increased SIRT1 activity further. In contrast, the level of adenosine triphosphate (ATP) was reduced in the restraint model for depression, and recovered by the administration of NAM. Furthermore, the Sirt1flox/flox; Nestin-Cre mice exhibited antidepressant behaviors and increased ATP levels. These data suggest that ATP plays an important role in depression pathogenesis, and NAM could be a potential treatment method for depression by regulating ATP independent of SIRT1 activity.

Original languageEnglish
Article number162
JournalMolecular Brain
Issue number1
Publication statusPublished - Dec 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience


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