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Sleep architecture changes in the APP23 mouse model manifest at onset of cognitive deficits.
Behav Brain Res 2019; 373:112089BB

Abstract

Alzheimer's disease (AD), which accounts for most of the dementia cases, is, aside from cognitive deterioration, often characterized by the presence of non-cognitive symptoms such as activity and sleep disturbances. AD patients typically experience increased sleep fragmentation, excessive daytime sleepiness and night-time insomnia. Here, we sought to investigate the link between sleep architecture, cognition and amyloid pathology in the APP23 amyloidosis mouse model for AD. By means of polysomnographic recordings the sleep-wake cycle of freely-moving APP23 and wild-type (WT) littermates of 3, 6 and 12 months of age was examined. In addition, ambulatory cage activity was assessed by interruption of infrared beams surrounding the home cage. To assess visuo-spatial learning and memory a hidden-platform Morris-type Water Maze (MWM) experiment was performed. We found that sleep architecture is only slightly altered at early stages of pathology, but significantly deteriorates from 12 months of age, when amyloid plaques become diffusely present. APP23 mice of 12 months old had quantitative reductions of NREM and REM sleep and were more awake during the dark phase compared to WT littermates. These findings were confirmed by increased ambulatory cage activity during that phase of the light-dark cycle. No quantitative differences in sleep parameters were observed during the light phase. However, during this light phase, the sleep pattern of APP23 mice was more fragmented from 6 months of age, the point at which also cognitive abilities started to be affected in the MWM. Sleep time also positively correlated with MWM performance. We also found that spectral components in the EEG started to alter at the age of 6 months. To conclude, our results indicate that sleep architectural changes arise around the time the first amyloid plaques start to form and cognitive deterioration becomes apparent. These changes start subtle, but gradually worsen with age, adequately mimicking the clinical condition.

Authors+Show Affiliations

Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, Department of Biomedical Sciences, University of Antwerp, Wilrijk (Antwerp), Belgium.Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, Department of Biomedical Sciences, University of Antwerp, Wilrijk (Antwerp), Belgium; Department of Neurology and Alzheimer Center, University of Groningen and University Medical Center Groningen (UMCG), Groningen, the Netherlands.Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, Department of Biomedical Sciences, University of Antwerp, Wilrijk (Antwerp), Belgium.Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, Department of Biomedical Sciences, University of Antwerp, Wilrijk (Antwerp), Belgium; Department of Neurology and Alzheimer Center, University of Groningen and University Medical Center Groningen (UMCG), Groningen, the Netherlands; Department of Neurology, Memory Clinic of Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium. Electronic address: p.p.de.deyn@umcg.nl.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31325518

Citation

Van Erum, Jan, et al. "Sleep Architecture Changes in the APP23 Mouse Model Manifest at Onset of Cognitive Deficits." Behavioural Brain Research, vol. 373, 2019, p. 112089.
Van Erum J, Van Dam D, Sheorajpanday R, et al. Sleep architecture changes in the APP23 mouse model manifest at onset of cognitive deficits. Behav Brain Res. 2019;373:112089.
Van Erum, J., Van Dam, D., Sheorajpanday, R., & De Deyn, P. P. (2019). Sleep architecture changes in the APP23 mouse model manifest at onset of cognitive deficits. Behavioural Brain Research, 373, p. 112089. doi:10.1016/j.bbr.2019.112089.
Van Erum J, et al. Sleep Architecture Changes in the APP23 Mouse Model Manifest at Onset of Cognitive Deficits. Behav Brain Res. 2019 Nov 5;373:112089. PubMed PMID: 31325518.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sleep architecture changes in the APP23 mouse model manifest at onset of cognitive deficits. AU - Van Erum,Jan, AU - Van Dam,Debby, AU - Sheorajpanday,Rishi, AU - De Deyn,Peter Paul, Y1 - 2019/07/17/ PY - 2019/05/07/received PY - 2019/06/26/revised PY - 2019/07/16/accepted PY - 2019/7/22/pubmed PY - 2019/7/22/medline PY - 2019/7/21/entrez KW - APP23 KW - Cognition KW - EEG KW - Locomotor activity KW - Morris water maze KW - Sleep SP - 112089 EP - 112089 JF - Behavioural brain research JO - Behav. Brain Res. VL - 373 N2 - Alzheimer's disease (AD), which accounts for most of the dementia cases, is, aside from cognitive deterioration, often characterized by the presence of non-cognitive symptoms such as activity and sleep disturbances. AD patients typically experience increased sleep fragmentation, excessive daytime sleepiness and night-time insomnia. Here, we sought to investigate the link between sleep architecture, cognition and amyloid pathology in the APP23 amyloidosis mouse model for AD. By means of polysomnographic recordings the sleep-wake cycle of freely-moving APP23 and wild-type (WT) littermates of 3, 6 and 12 months of age was examined. In addition, ambulatory cage activity was assessed by interruption of infrared beams surrounding the home cage. To assess visuo-spatial learning and memory a hidden-platform Morris-type Water Maze (MWM) experiment was performed. We found that sleep architecture is only slightly altered at early stages of pathology, but significantly deteriorates from 12 months of age, when amyloid plaques become diffusely present. APP23 mice of 12 months old had quantitative reductions of NREM and REM sleep and were more awake during the dark phase compared to WT littermates. These findings were confirmed by increased ambulatory cage activity during that phase of the light-dark cycle. No quantitative differences in sleep parameters were observed during the light phase. However, during this light phase, the sleep pattern of APP23 mice was more fragmented from 6 months of age, the point at which also cognitive abilities started to be affected in the MWM. Sleep time also positively correlated with MWM performance. We also found that spectral components in the EEG started to alter at the age of 6 months. To conclude, our results indicate that sleep architectural changes arise around the time the first amyloid plaques start to form and cognitive deterioration becomes apparent. These changes start subtle, but gradually worsen with age, adequately mimicking the clinical condition. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/31325518/Sleep_architecture_changes_in_the_APP23_mouse_model_manifest_at_onset_of_cognitive_deficits L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(19)30710-7 DB - PRIME DP - Unbound Medicine ER -