ArticleJournal of Alzheimer's disease : JAD2021
Evaluation of SAMP8 Mice as a Model for Sleep-Wake and Rhythm Disturbances Associated with Alzheimer's Disease: Impact of Treatment with the Dual Orexin (Hypocretin) Receptor Antagonist Lemborexant.
Article in Journal of Alzheimer's disease : JAD, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Sleep disruption with aging in senescence-accelerated mice-prone 8 (SAMP8) mice and analysis of factors associated with age-related sleep fragmentation using RNA sequencing of the hypothalamus.Neurobiology of sleep and circadian rhythms · 2026Article
- The orexin/hypocretin system in dementia-related neurological disorders: a double-edged sword in cognitive impairment.Psychopharmacology · 2025Review
- Exogenous Nucleotides Mitigate Cardiac Aging in SAMP8 Mice by Modulating Energy Metabolism Through AMPK Pathway.Nutrients · 2024Article
- Article
- Diurnal Characteristics of the Orexin System Genes and Its Effects on Pathology at Early Stage in 3xTg-AD Mice.Neuromolecular medicine · 2023Article
- Progressive sleep disturbance in various transgenic mouse models of Alzheimer's disease.Frontiers in aging neuroscience · 2023Review
- Probing the relevance of the accelerated aging mouse line SAMP8 as a model for certain types of neuropsychiatric symptoms in dementia.Frontiers in psychiatry · 2023Article
- Differential sleep/wake response and sex differences following acute suvorexant, MK-1064 and zolpidem administration in the rTg4510 mouse model of tauopathy.British journal of pharmacology · 2022Article
- Circadian disruption of hippocampus in an early senescence male mouse model.Pharmacology, biochemistry, and behavior · 2022Article
- A Growing Link between Circadian Rhythms, Type 2 Diabetes Mellitus and Alzheimer's Disease.International journal of molecular sciences · 2022Review
- What evidence is there for implicating the brain orexin system in neuropsychiatric symptoms in dementia?Frontiers in psychiatry · 2022Article
- Effect of a dual orexin receptor antagonist on Alzheimer's disease: Sleep disorders and cognition.Frontiers in medicine · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMany patients with Alzheimer's disease (AD) display circadian rhythm and sleep-wake disturbances. However, few mouse AD models exhibit these disturbances. Lemborexant, a dual orexin receptor antagonist, is under development for treating circadian rhythm disorders in dementia.
objectiveEvaluation of senescence-accelerated mouse prone-8 (SAMP8) mice as a model for sleep-wake and rhythm disturbances in AD and the effect of lemborexant by assessing sleep-wake/diurnal rhythm behavior.
methodsSAMP8 and control senescence-accelerated mouse resistant-1 (SAMR1) mice received vehicle or lemborexant at light onset; plasma lemborexant and diurnal cerebrospinal fluid (CSF) orexin concentrations were assessed. Sleep-wake behavior and running wheel activity were evaluated.
resultsPlasma lemborexant concentrations were similar between strains. The peak/nadir timing of CSF orexin concentrations were approximately opposite between strains. During lights-on, SAMP8 mice showed less non-rapid eye movement (non-REM) and REM sleep than SAMR1 mice. Lemborexant treatment normalized wakefulness/non-REM sleep in SAMP8 mice. During lights-off, lemborexant-treated SAMR1 mice showed increased non-REM sleep; lemborexant-treated SAMP8 mice displayed increased wakefulness. SAMP8 mice showed differences in electroencephalogram architecture versus SAMR1 mice. SAMP8 mice exhibited more running wheel activity during lights-on. Lemborexant treatment reduced activity during lights-on and increased activity in the latter half of lights-off, demonstrating a corrective effect on overall diurnal rhythm. Lemborexant delayed the acrophase of activity in both strains by approximately 1 hour.
conclusionSAMP8 mice display several aspects of sleep-wake and rhythm disturbances in AD, notably mistimed activity. These findings provide some preclinical rationale for evaluating lemborexant in patients with AD who experience sleep-wake and rhythm disturbances.
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