Nicotinamide mononucleotide pretreatment improves long-term isoflurane anesthesia-induced cognitive impairment in mice.

Abstract

Postoperative cognitive dysfunction (POCD) is characterized by impaired cognitive function following general anesthesia and surgery. Oxidative stress is a significant pathophysiological manifestation underlying POCD. Previous studies have reported that the decline of nicotinamide adenine dinucleotide (NAD+) -dependent sirtuin 1 (SIRT1) contributes to the activation of oxidative stress. In this study, we investigated whether pretreatment of nicotinamide mononucleotide (NMN), an NAD+ intermediate, improves oxidative stress and cognitive function in POCD. The animal model of POCD was established in C57BL/6 J mice through 6 h isoflurane anesthesia-induced cognitive impairment. Mice were intraperitoneally injected with NMN for 7 days prior to anesthesia, after which oxidative stress and cognitive function were assessed. The level of oxidative stress was determined using flow cytometry analysis and assey kits. The fear condition test and the Y-maze test were utilized to evaluate contextual and spatial memory. Our results showed that cognitive impairment and increased oxidative stress were observed in POCD mice, as well as downregulation of NAD+ levels and related protein expressions of SIRT1 and nicotinamide phosphoribosyltransferase (NAMPT) in the hippocampus. And NMN supplementation could effectively prevent the decline of NAD+ and related proteins, and reduce oxidative stress and cognitive disorders after POCD. Mechanistically, the findings suggested that protection on cognitive function mediated by NMN pretreatment in POCD mice may be regulated by NAD+-SIRT1 signaling pathway. This study indicated that NMN preconditioning reduced oxidative stress damage and alleviated cognitive impairment in POCD mice.

• Authors: Jiyan Xu, Xinlu Chen, Shuai Liu, Ziqi Wei, Minhui Xu, Linhao Jiang, Xue Han, Liangyu Peng, Xiaoping Gu, Tianjiao Xia
• Journal: Behavioural brain research (Behav Brain Res) Vol. 458 Pg. 114738 (Feb 26 2024) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 37931707 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Nicotinamide Mononucleotide
• NAD
• Isoflurane
• Sirtuin 1

Topics

• Mice
• Animals
• Nicotinamide Mononucleotide (pharmacology, metabolism)
• NAD
• Isoflurane
• Sirtuin 1 (metabolism)
• Mice, Inbred C57BL
• Cognitive Dysfunction (chemically induced)
• Anesthesia