Division of Neurology, Department of Medicine, Hurvitz Brain Sciences Program, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
Alzheimers Dement. 2023 May;19(5):1888-1900. doi: 10.1002/alz.12817. Epub 2022 Nov 6.
Sleep disruption is associated with astrocyte activation and impaired cognition in model organisms. However, the relationship among sleep, astrocyte activation, and cognition in humans is uncertain.
We used RNA-seq to quantify the prefrontal cortex expression of a panel of human activated astrocyte marker genes in 1076 older adults in the Religious Orders Study and Rush Memory and Aging Project, 411 of whom had multi-day actigraphy prior to death. We related this to rest fragmentation, a proxy for sleep fragmentation, and to longitudinal cognitive function.
Fragmentation of rest periods was associated with higher expression of activated astrocyte marker genes, which was associated with a lower level and faster decline of cognitive function.
Astrocyte activation and fragmented rest are associated with each other and with accelerated cognitive decline. If experimental studies confirm a causal relationship, targeting sleep fragmentation and astrocyte activation may benefit cognition in older adults.
Greater fragmentation of rest periods, a proxy for sleep fragmentation, is associated with higher composite expression of a panel of genes characteristic of activated astrocytes. Increased expression of genes characteristic of activated astrocytes was associated with a lower level and more rapid decline of cognitive function, beyond that accounted for by the burden of amyloid and neurofibrillary tangle pathology. Longitudinal and experimental studies are needed to delineate the causal relationships among sleep, astrocyte activation, and cognition.
睡眠中断与模型生物中的星形胶质细胞激活和认知障碍有关。然而，人类睡眠、星形胶质细胞激活和认知之间的关系尚不确定。
我们使用 RNA-seq 技术在宗教秩序研究和拉什记忆与衰老项目中对 1076 名老年人大脑中前额叶皮层的一组人类激活星形胶质细胞标记基因的表达进行了定量分析，其中 411 人在死亡前进行了多天的活动记录仪检测。我们将其与休息片段化（睡眠片段化的替代指标）和纵向认知功能联系起来。
休息时间的碎片化与激活的星形胶质细胞标记基因的表达更高有关，而这些基因的表达与认知功能的水平更低和下降更快有关。
星形胶质细胞的激活和碎片化的休息与彼此以及与认知功能的加速下降有关。如果实验研究证实存在因果关系，那么针对睡眠碎片化和星形胶质细胞激活可能会使老年人受益于认知功能。
休息时间碎片化（睡眠碎片化的替代指标）越大，与一组特征性激活星形胶质细胞的基因的综合表达越高。特征性激活星形胶质细胞基因的表达增加与认知功能的水平更低和下降更快有关，超过了淀粉样蛋白和神经原纤维缠结病理学负担所解释的程度。需要进行纵向和实验研究来阐明睡眠、星形胶质细胞激活和认知之间的因果关系。
