1. Dual orexin receptor antagonist ameliorates sleep deprivation-induced learning and memory impairment in APP/PS1 mice.
- Author
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Li Y, Yan Z, Shao N, Tang S, Zhang X, Liu XM, and Tang J
- Subjects
- Animals, Mice, Isoquinolines pharmacology, Isoquinolines therapeutic use, Amyloid beta-Protein Precursor genetics, Acetamides pharmacology, Acetamides therapeutic use, Male, Amyloid beta-Peptides metabolism, Learning drug effects, Cognitive Dysfunction drug therapy, Cognitive Dysfunction etiology, Orexin Receptors metabolism, Presenilin-1 genetics, Sleep Deprivation complications, Sleep Deprivation drug therapy, Orexin Receptor Antagonists pharmacology, Orexin Receptor Antagonists therapeutic use, Alzheimer Disease drug therapy, Alzheimer Disease complications, Disease Models, Animal, Memory Disorders drug therapy, Memory Disorders etiology, Mice, Transgenic
- Abstract
Sleep is considered closely related to cognitive function, and cognitive impairment is the main clinical manifestation of Alzheimer's disease (AD). Sleep disturbance in AD patients is more severe than that in healthy elderly individuals. Additionally, sleep deprivation reportedly increases the activity of the hypothalamic orexin system and the risk of AD. To investigate whether intervention with the orexin system can improve sleep disturbance in AD and its impact on AD pathology. In this study, six-month-old amyloid precursor protein/presenilin 1 mice were subjected to six weeks of chronic sleep deprivation and injected intraperitoneally with almorexant, a dual orexin receptor antagonist (DORA), to investigate the effects and mechanisms of sleep deprivation and almorexant intervention on learning and memory in mice with AD. We found that sleep deprivation aggravated learning and memory impairment and increased brain β-amyloid (Aβ) deposition in mice with AD. The application of almorexant can increase the total sleep time of sleep-deprived mice and reduce cognitive impairment and Aβ deposition, which is related to the improvement in Aquaporin-4 polarity. Thus, DORA may be an effective strategy for delaying the progression of AD patients by improving the sleep disturbances., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
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