期刊
FRONTIERS IN NEUROSCIENCE
卷 16, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2022.938874
关键词
postoperative cognitive dysfunction; nobiletin; clock gene; neuroinflammation; surgery
资金
- Peking University Third Hospital [Y85477-01]
- National Natural Science Foundation of China [820071189, 81901095, 81873726, 81971012]
- Beijing Natural Science Foundation [7212131]
- Interdisciplinary Medicine Seed Fund of Peking University [BMU2021MX026]
Postoperative cognitive dysfunction (POCD) is a common and significant issue that affects the prognosis of patients after surgery. Neuroinflammation plays a crucial role in the pathogenesis of POCD. Despite the lack of practical pharmacological strategies for the treatment and prevention of POCD, this study found that the natural polymethoxylated flavone Nobiletin (NOB) may be a candidate for these purposes.
Postoperative cognitive dysfunction (POCD) is commonly observed during the postoperative period and significantly affects the prognosis of patients. Neuroinflammation plays a vital role in the pathogenesis of POCD. Despite laboratory and clinical research over the past decades, practical pharmacological strategies for the treatment and prevention of POCD are not yet available currently. Nobiletin (NOB) is a natural polymethoxylated flavone. As an enhancer of the clock protein retinoic acid receptor-related orphan receptors (RORs), NOB has been shown to attenuate inflammation and improve cognitive decline. We speculate that NOB is a candidate for the treatment and prevention of POCD. In this study, we investigated whether and how NOB affected surgery-induced neuroinflammation and POCD in adult CD1 mice. NOB pretreatment suppressed exploratory laparotomy-induced systemic inflammation and neuroinflammation in a dose-dependent manner (< 50 mg/kg), and attenuated POCD. Moreover, NOB dose-dependently reversed the decrease of brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1, also known as Arntl) and Rors expression induced by exploratory laparotomy. The expression of Bmal was negatively correlated with tumor necrosis factor-alpha (TNF-alpha). Our results suggest that NOB attenuated POCD, possibly via preserving the expression of Bmal and Rors and inhibiting inflammation.
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