Bio-X Institutes, Key Laboratory for the Genetics of Development and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Institute of Psychology and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai, 200240, China.
Mol Brain. 2020 Nov 23;13(1):162. doi: 10.1186/s13041-020-00703-4.
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 Sirt1; 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.
Sirtuin 1 (SIRT1) 是一种烟酰胺腺嘌呤二核苷酸 (NAD) 依赖性蛋白去乙酰化酶，也是抑郁症的候选基因。烟酰胺 (NAM)，一种维生素 B3 的形式，被报道为 SIRT1 的潜在抑制剂。我们之前的研究发现，24 小时束缚应激可以诱导小鼠产生长期的抑郁样表型。这些小鼠表现出 SIRT1 活性增加。在这里，我们研究了 NAM 是否能够通过抑制 SIRT1 活性来减轻抑郁行为。令人惊讶的是，NAM 的应用显著逆转了抑郁行为，但进一步增加了 SIRT1 的活性。相比之下，在抑郁的束缚模型中，三磷酸腺苷 (ATP) 的水平降低，而 NAM 的给药则使其恢复。此外，Sirt1;Nestin-Cre 小鼠表现出抗抑郁行为和增加的 ATP 水平。这些数据表明，ATP 在抑郁症发病机制中起着重要作用，NAM 可以通过调节与 SIRT1 活性无关的 ATP 成为一种潜在的抑郁症治疗方法。
