Dexmedetomidine improves sleep quality and alleviates emotional dysfunction by attenuating α-synuclein deposition in mice with sepsis-associated encephalopathy

作者：Qi Jia, Lin Yang, Jiajia Wang, Jin Li, Lixia Du, Yong‐Sheng Chen, Yi Li, Zongping Fang, Xijing Zhang · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.07.012 · 被引用次数：4 · 研究领域：Sleep and related disorders、Sleep and Wakefulness Research、Intensive Care Unit Cognitive Disorders

Introduction Most septic patients have severe sleep disorders that are closely related to poor prognoses, and some patients with sepsis-associated encephalopathy (SAE) experience severe cerebral inflammatory reactions similar to those in neurodegenerative disease. α-synuclein, a widely expressed synaptic protein whose abnormal deposition can lead to neurodegenerative diseases, was also observed to be deposited abnormally in an SAE mouse model. Objectives Sleep disorders are common in SAE patients and are strongly associated with prognoses. Our aim is to clarify sleep architecture changes, investigate the link between sleep and α-synuclein deposition, and identify new target for SAE treatment. Methods Injection of lipopolysaccharide i.cv and cecum ligation and puncture were used to establish SAE models. The telemetric implantation system was used to record electroencephalogram and electromyography signals of animals. Biological signal analysis, behavioral tests and molecular biology techniques were employed to investigate the relationship among sleep, α-synuclein, and emotional dysfunction of SAE mice. In addition, dexmedetomidine (50 ug kg −1 , i.p.) was used for treatment to investigate its effects on sleep quality and prognosis of SAE. Results SAE mice exhibited severe sleep fragmentation, including increased frequency of sleep and wakefulness, and decreased sleep quality. Fragmented sleep leading to α-synuclein deposition in the hippocampus, and developed anxiety and depre...