β-Nicotinamide mononucleotide activates NAD+/SIRT1 pathway and attenuates inflammatory and oxidative responses in the hippocampus regions of septic mice

作者：Hui-ru Li, Qiang Liu, Cheng‐long Zhu, Xiaoyang Sun, Chen-yan Sun, Chang-meng Yu, Peng Li, Xiaoming Deng, Jiafeng Wang · 发表于：Redox Biology · 年份：2023 · DOI：10.1016/j.redox.2023.102745 · 被引用次数：160 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Sirtuins and Resveratrol in Medicine、Medicinal Plants and Bioactive Compounds

Sepsis-associated encephalopathy (SAE) is one of the common serious complications in sepsis, and the pathogenesis of SAE remains unclear. Sirtuin 1 (SIRT1) has been reported to be downregulated in the hippocampus and SIRT1 agonists can attenuated the cognitive dysfunction in septic mice. Nicotinamide adenine dinucleotide (NAD+) is a key substrate to maintain the deacetylation activity of SIRT1. As an intermediate of NAD+, β-Nicotinamide Mononucleotide (NMN) has been reported to be promising in treating neurodegenerative diseases and cerebral ischemic injury. Thus we sought to investigate the potential role of NMN in SAE treatment. The SAE model was established by cecal ligation and puncture (CLP) in vivo, and neuroinflammation model was established with LPS-treated BV-2 cells in vitro. Memory impairment was assessed by Morris water maze and fear conditioning tests. As a result, the levels of NAD+, SIRT1 and PGC-1α were significantly reduced in the hippocampus of septic mice, while the acetylation of total lysine, phosphorylation of P38 and P65 were enhanced. All these changes induced by sepsis were inverted by NMN. Treating with NMN resulted in improved behavior performance in the fear conditioning tests and Morris water maze. Apoptosis, inflammatory and oxidative responses in the hippocampus of septic mice were attenuated significantly after NMN administration. These protective effect of NMN against memory dysfunction, inflammatory and oxidative injuries were reversed by the...