Effects of aging and genotype on circadian rhythms, sleep, and clock gene expression in APPxPS1 knock-in mice, a model for Alzheimer's disease

Duncan, Marilyn J.; Smith, Jeff; Franklin, Kathleen M.; Beckett, Tina L.; Murphy, Michael P.; Clair, Daret K. St.; Donohue, Kevin D.; Striz, Martin; O’Hara, Bruce F.

doi:10.1016/j.expneurol.2012.05.011

Cited by 91 publications

(70 citation statements)

References 35 publications

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“…It is difficult to make direct comparisons as the rodent species, age, method of expression measurement, time-point and brain tissue sampling technique differs from the present study. The study by (32) found a significant upregulation of Per2 expression in the SCN at ZT10 compared to ZT2 in APPSwe/PS1dE9 mice, which agrees with our findings in WT mice only. One crucial difference from the present study is a different background strain of mouse [c57BL/6 vs CD1/129].…”

Section: Discussionsupporting

confidence: 92%

“…There was no effect of genotype on any of the clock genes investigated in the hippocampus. Similarly, (32) found that Per2 expression in the hippocampus, cingulate cortex and motor cortex were not significantly affected by genotype or time of day. The overall expression level of clock genes relative to GAPDH was significantly lower in the hippocampus compared to the medulla/pons, which may have made it more difficult to detect changes, however we did show a clear day/night increase for Per1, Per2 and Rev-erb.…”

Section: Discussionmentioning

confidence: 82%

“…Percentage of the first/last 2 hours in the light/dark period refers to the percentage of total daily activity occurring in the first/last 2 hours of the light/dark phases (32). Period length was calculated using the Chi (37) .…”

Section: Analysis Of Locomotor Activity Datamentioning

confidence: 99%

“…Duncan and colleagues (32) showed the clock gene Per2 is increased at night in the SCN of wild-type mice with a strong trend towards attenuation of this increase in APPxPS1 mice that did not reach statistical significance. The mice used in that study were on a CD1/129 background strain and notably did not show the hyperactivity frequently reported in APPxPS1 mice.…”

mentioning

confidence: 97%

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Abnormal Clock Gene Expression and Locomotor Activity Rhythms in Two Month-Old Female APPSwe/PS1dE9 Mice

Oyegbami

Collins

Pardon

et al. 2017

CAR

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 82%

Section: Analysis Of Locomotor Activity Datamentioning

confidence: 99%

mentioning

confidence: 97%

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Abnormal Clock Gene Expression and Locomotor Activity Rhythms in Two Month-Old Female APPSwe/PS1dE9 Mice

Oyegbami

Collins

Pardon

et al. 2017

CAR

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“…Likewise, the doubly transgenic model SPPswe/PS1dE9 mouse (up to 7 months of age) does not display marked abnormalities in its circadian organization of behavior, although there is an increase in daytime core body temperature compared with wildtypes (69). The APPxPS1 mouse displays a phase delay of its daytime wakefulness bout, although most parameters of the activity rhythms were not altered (70). Furthermore, old APPxPS1 animals displayed blunted diurnal variation in the SCN expression of Per2.…”

Section: An Coogan Et Almentioning

confidence: 96%

The Circadian System in Alzheimer’s Disease: Disturbances, Mechanisms, and Opportunities

Coogan

Schutová

Husung

et al. 2013

Biological Psychiatry

146

131

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Alzheimer's disease (AD) is a devastating neurodegenerative condition associated with severe cognitive and behavioral impairments. Circadian rhythms are recurring cycles that display periods of approximately 24 hours and are driven by an endogenous circadian timekeeping system centered on the suprachiasmatic nucleus of the hypothalamus. We review the compelling evidence that circadian rhythms are significantly disturbed in AD and that such disturbance is of significant clinical importance in terms of behavioral symptoms. We also detail findings from neuropathological studies of brain areas associated with the circadian system in postmortem studies, the use of animal models of AD in the investigation of circadian processes, and the evidence that chronotherapeutic approaches aimed at bolstering weakened circadian rhythms in AD produce beneficial outcomes. We argue that further investigation in such areas is warranted and highlight areas for future research that might prove fruitful in ultimately providing new treatment options for this most serious and intractable of conditions.

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Experimental diffuse brain injury and a model of Alzheimer's disease exhibit disease‐specific changes in sleep and incongruous peripheral inflammation

Saber

Murphy

Cho

et al. 2020

J of Neuroscience Research

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Elderly populations (≥65 years old) have the highest risk of developing Alzheimer's disease (AD) and/or obtaining a traumatic brain injury (TBI). Using translational mouse models, we investigated sleep disturbances and inflammation associated with normal aging, TBI and aging, and AD. We hypothesized that aging results in marked changes in sleep compared with adult mice, and that TBI and aging would result in sleep and inflammation levels similar to AD mice. We used female 16-month-old wild-type (WT Aged) and 3xTg-AD mice, as well as a 2-month-old reference group (WT Adult), to evaluate sleep changes. WT Aged mice received diffuse TBI by midline fluid percussion, and blood was collected from both WT Aged (pre-and post-TBI) and 3xTg-AD mice to evaluate inflammation. Cognitive behavior was tested, and tissue was collected for histology. Bayesian generalized additive and mixed-effects models were used for analyses. Both normal aging and AD led to increases in sleep compared with adult mice. WT Aged mice with TBI slept substantially more, with fragmented shorter bouts, than they did pre-TBI and compared with AD mice. However, differences between WT Aged and 3xTg-AD mice in immune cell populations and plasma cytokine levels were incongruous, cognitive deficits were similar, and cumulative sleep was not predictive of inflammation or behavior for either group. Our results suggest that in similarly aged individuals, TBI immediately induces more profound sleep alterations than in AD, although both diseases likely include cognitive impairments. Unique pathological sleep pathways may exist in elderly individuals who incur TBI compared with similarly aged individuals who have AD, which may warrant disease-specific treatments in clinical settings.

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Effects of aging and genotype on circadian rhythms, sleep, and clock gene expression in APPxPS1 knock-in mice, a model for Alzheimer's disease

Cited by 91 publications

References 35 publications

Abnormal Clock Gene Expression and Locomotor Activity Rhythms in Two Month-Old Female APPSwe/PS1dE9 Mice

Abnormal Clock Gene Expression and Locomotor Activity Rhythms in Two Month-Old Female APPSwe/PS1dE9 Mice

The Circadian System in Alzheimer’s Disease: Disturbances, Mechanisms, and Opportunities

Experimental diffuse brain injury and a model of Alzheimer's disease exhibit disease‐specific changes in sleep and incongruous peripheral inflammation

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