TY - JOUR
T1 - Nicotinamide, a vitamin B3 ameliorates depressive behaviors independent of SIRT1 activity in mice
AU - Liu, Zhuxi
AU - Li, Caiqin
AU - Fan, Xuelian
AU - Kuang, Yifang
AU - Zhang, Xu
AU - Chen, Lei
AU - Song, Jinjing
AU - Zhou, Ying
AU - Takahashi, Eiki
AU - He, Guang
AU - Li, Weidong
N1 - Funding Information:
This study is supported by Shanghai Education Commission Research and Innovation Program (2019-01-07-00-02-E00037), National Key Research and Development Program of China (2018YFE0126700), Program of Shanghai Subject Chief Scientist (17XD1401700), “111” Program of Higher Education Discipline Innovation, and Shanghai Jiao Tong University Scientific and Technological Innovation Funds.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
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U2 - 10.1186/s13041-020-00703-4
DO - 10.1186/s13041-020-00703-4
M3 - Article
C2 - 33228716
AN - SCOPUS:85096530767
SN - 1756-6606
VL - 13
JO - Molecular Brain
JF - Molecular Brain
IS - 1
M1 - 162
ER -