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Article

Clock/Sleep-Dependent Learning and Memory in Male 3xTg-AD Mice at Advanced Disease Stages and Extrinsic Effects of Huprine X and the Novel Multitarget Agent AVCRI104P3

1
Department of Psychiatry and Forensic Medicine & Institut de Neurociències, Universitat Autònoma de Barcelona, E-08193 Barcelona, Spain
2
Department of Pharmacology, Therapeutics and Toxicology & Institut de Neurociències, Universitat Autònoma de Barcelona, E-08193 Barcelona, Spain
3
CSIC Associated Unit, Laboratory of Medicinal Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Biomedicine (IBUB), University of Barcelona, E-08028 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Academic Editor: Luigi De Gennaro
Brain Sci. 2021, 11(4), 426; https://doi.org/10.3390/brainsci11040426
Received: 29 January 2021 / Revised: 16 March 2021 / Accepted: 23 March 2021 / Published: 26 March 2021
(This article belongs to the Special Issue Sleep in Healthy and Pathological Aging)
A new hypothesis highlights sleep-dependent learning/memory consolidation and regards the sleep-wake cycle as a modulator of β-amyloid and tau Alzheimer’s disease (AD) pathologies. Sundowning behavior is a common neuropsychiatric symptom (NPS) associated with dementia. Sleep fragmentation resulting from disturbances in sleep and circadian rhythms in AD may have important consequences on memory processes and exacerbate the other AD-NPS. The present work studied the effect of training time schedules on 12-month-old male 3xTg-AD mice modeling advanced disease stages. Their performance in two paradigms of the Morris water maze for spatial-reference and visual-perceptual learning and memory were found impaired at midday, after 4 h of non-active phase. In contrast, early-morning trained littermates, slowing down from their active phase, exhibited better performance and used goal-directed strategies and non-search navigation described for normal aging. The novel multitarget anticholinesterasic compound AVCRI104P3 (0.6 µmol·kg−1, 21 days i.p.) exerted stronger cognitive benefits than its in vitro equipotent dose of AChEI huprine X (0.12 μmol·kg−1, 21 days i.p.). Both compounds showed streamlined drug effectiveness, independently of the schedule. Their effects on anxiety-like behaviors were moderate. The results open a question of how time schedules modulate the capacity to respond to task demands and to assess/elucidate new drug effectiveness. View Full-Text
Keywords: sleep; circadian activity; protocols; behavior; drug assessment; aging; Alzheimer’s disease; BPSD; AChEI; multitarget compounds; disease-modifying mechanisms sleep; circadian activity; protocols; behavior; drug assessment; aging; Alzheimer’s disease; BPSD; AChEI; multitarget compounds; disease-modifying mechanisms
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MDPI and ACS Style

Giménez-Llort, L.; Santana-Santana, M.; Ratia, M.; Pérez, B.; Camps, P.; Muñoz-Torrero, D.; Badia, A.; Clos, M.V. Clock/Sleep-Dependent Learning and Memory in Male 3xTg-AD Mice at Advanced Disease Stages and Extrinsic Effects of Huprine X and the Novel Multitarget Agent AVCRI104P3. Brain Sci. 2021, 11, 426. https://doi.org/10.3390/brainsci11040426

AMA Style

Giménez-Llort L, Santana-Santana M, Ratia M, Pérez B, Camps P, Muñoz-Torrero D, Badia A, Clos MV. Clock/Sleep-Dependent Learning and Memory in Male 3xTg-AD Mice at Advanced Disease Stages and Extrinsic Effects of Huprine X and the Novel Multitarget Agent AVCRI104P3. Brain Sciences. 2021; 11(4):426. https://doi.org/10.3390/brainsci11040426

Chicago/Turabian Style

Giménez-Llort, Lydia, Mikel Santana-Santana, Míriam Ratia, Belén Pérez, Pelayo Camps, Diego Muñoz-Torrero, Albert Badia, and Maria V. Clos 2021. "Clock/Sleep-Dependent Learning and Memory in Male 3xTg-AD Mice at Advanced Disease Stages and Extrinsic Effects of Huprine X and the Novel Multitarget Agent AVCRI104P3" Brain Sciences 11, no. 4: 426. https://doi.org/10.3390/brainsci11040426

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