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

🎖️ Top 10% JournalSep 11, 2025Experimental neurology

Suvorexant may reduce thinking problems linked to sleep-wake cycle disorders by controlling brain immune cell activity through the BMAL1/NLRP3 pathway

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Suvorexant treatment significantly decreased sleep latency and escape latency while increasing sleep time in a rat model of circadian rhythm sleep-wake disorders.

Suvorexant enhanced swimming speed, the number of crossings, and time spent in each quadrant in the CRSD group.
The treatment upregulated levels of BMAL1, IL-10, CD206, and TGF-β in CRSD rats.
It downregulated levels of NLRP3, IL-1β, Aβ1-40, Aβ1-42, IL-6, TNF-α, and iNOS.
The reversal of suvorexant's effects by sh-BMAL1 intervention suggests a role for BMAL1 in cognitive impairment in CRSD rats.
Suvorexant may influence cognitive impairment through modulation of microglial activation and the BMAL1/NLRP3 pathway.

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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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