Suvorexant通过BMAL1/NLRP3通路调节小胶质细胞激活，减轻与昼夜节律睡眠-觉醒障碍相关的认知障碍。

IF 4.2 2区医学 Q1 NEUROSCIENCES

Experimental Neurology Pub Date : 2025-09-09 DOI:10.1016/j.expneurol.2025.115464

Yujie Hu , Tian Yun , Dan Hou, Guoshuai Yang

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引用次数: 0

摘要

背景：昼夜节律睡眠-觉醒障碍（CRSD）和认知障碍是许多神经系统疾病的共同特征。Suvorexant是一种治疗失眠的新药。本研究旨在探讨抗抑郁药在缓解CRSD中的作用及其潜在机制。方法：对光热位移诱导的CRSD模型大鼠进行舒维适治疗，观察其对认知功能、BMAL1/NLRP3轴相关基因、小胶质细胞标志物IBA1、Aβ水平及炎症因子表达的影响。随后，我们利用海马传递sh-BMAL1来研究过度药缓解CRSD模型的具体机制。结果：强效治疗显著降低了睡眠潜伏期和逃避潜伏期，增加了CRSD组的睡眠时间、游泳速度、穿越次数和每个象限的时间。此外，我们发现Suvorexant上调CRSD大鼠BMAL1、IL-10、CD206和TGF-β水平，下调NLRP3、IL-1β、a -β 1-40、a -β 1-42、IL-6、TNF-α和iNOS水平。sh-BMAL1干预逆转了suvorexant的作用，提示BMAL1可能在suvorexant如何影响CRSD大鼠的认知障碍中发挥作用。结论：Suvorexant可能通过调节小胶质细胞激活和BMAL1/NLRP3通路改善crsd相关认知障碍，为相关疾病的研究提供了潜在的见解。

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Suvorexant attenuates cognitive impairment associated with circadian rhythm sleep-wake disorders by modulating microglia activation via the BMAL1/NLRP3 pathway

Background

Circadian rhythm sleep-wake disorders (CRSD) and cognitive impairment are common features of many neurological disorders. Suvorexant is a novel drug for the treatment of insomnia. The study aimed to investigate the effects and potential mechanisms of suvorexant in alleviating CRSD.

Methods

The photothermal displacement-induced CRSD model rats were treated with suvorexant to investigate its impact on cognitive function, the BMAL1/NLRP3 axis-related genes, the microglial marker IBA1, Aβ levels, and the expression of inflammatory factors. Subsequently, hippocampal delivery of sh-BMAL1 was used to investigate the specific mechanism by which suvorexant alleviates the CRSD model.

Results

Suvorexant treatment significantly decreased sleep latency and escape latency, while increasing sleep time, swimming speed, the number of crossings, and the time spent in each quadrant in the CRSD group. Moreover, Suvorexant was found to upregulate the levels of BMAL1, IL-10, CD206, and TGF-β in CRSD rats, and downregulate the levels of NLRP3, IL-1β, Aβ1–40, Aβ1–42, IL-6, TNF-α, and iNOS. The sh-BMAL1 intervention reversed suvorexant's effects, suggesting that BMAL1 may play a role in how suvorexant influences cognitive impairment in CRSD rats.

Conclusion

Suvorexant may improve CRSD-related cognitive impairment by modulating microglial activation and the BMAL1/NLRP3 pathway, providing potential insights into related conditions.

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来源期刊

Experimental Neurology 医学-神经科学

CiteScore

10.10

自引率

3.80%

发文量

258

审稿时长

42 days

期刊介绍： Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.