Evaluating Circadian Dysfunction in Mouse Models of Alzheimer's Disease: Where Do We Stand?

Overview

Journal Front Neurosci

Date 2020 Aug 1

PMID 32733196

Citations 14

Authors

Patrick W Sheehan

Erik S Musiek

Affiliations

Soon will be listed here.

Abstract

Circadian dysfunction has been described in patients with symptomatic Alzheimer's disease (AD), as well as in presymptomatic phases of the disease. Modeling this circadian dysfunction in mouse models would provide an optimal platform for understanding mechanisms and developing therapies. While numerous studies have examined behavioral circadian function, and in some cases clock gene oscillation, in mouse models of AD, the results are variable and inconsistent across models, ages, and conditions. Ultimately, circadian changes observed in APP/PS1 models are inconsistent across studies and do not always replicate circadian phenotypes observed in human AD. Other models, including the 3xTG mouse, tau transgenic lines, and the accelerated aging SAMP8 line, show circadian phenotypes more consistent with human AD, although the literature is either inconsistent or minimal. We summarize these data and provide some recommendations to improve and standardize future studies of circadian function in AD mouse models.

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References

Knight E, Brown T, Gumusgoz S, Smith J, Waters E, Allan S . Age-related changes in core body temperature and activity in triple-transgenic Alzheimer's disease (3xTgAD) mice. Dis Model Mech. 2012; 6(1):160-70. PMC: 3529348. DOI: 10.1242/dmm.010173. View

Sun Y, Guo Y, Feng X, Jia M, Ai N, Dong Y . The behavioural and neuropathologic sexual dimorphism and absence of MIP-3α in tau P301S mouse model of Alzheimer's disease. J Neuroinflammation. 2020; 17(1):72. PMC: 7041244. DOI: 10.1186/s12974-020-01749-w. View

Swaab D, Fliers E, Partiman T . The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia. Brain Res. 1985; 342(1):37-44. DOI: 10.1016/0006-8993(85)91350-2. View

Ramsden M, Kotilinek L, Forster C, Paulson J, McGowan E, SantaCruz K . Age-dependent neurofibrillary tangle formation, neuron loss, and memory impairment in a mouse model of human tauopathy (P301L). J Neurosci. 2005; 25(46):10637-47. PMC: 6725849. DOI: 10.1523/JNEUROSCI.3279-05.2005. View

Ni J, Wu Z, Meng J, Saito T, Saido T, Qing H . An impaired intrinsic microglial clock system induces neuroinflammatory alterations in the early stage of amyloid precursor protein knock-in mouse brain. J Neuroinflammation. 2019; 16(1):173. PMC: 6716829. DOI: 10.1186/s12974-019-1562-9. View

Naismith S, Hickie I, Terpening Z, Rajaratnam S, Rajaratnam S, Hodges J . Circadian misalignment and sleep disruption in mild cognitive impairment. J Alzheimers Dis. 2013; 38(4):857-66. DOI: 10.3233/JAD-131217. View

Ma Z, Jiang W, Zhang E . Orexin signaling regulates both the hippocampal clock and the circadian oscillation of Alzheimer's disease-risk genes. Sci Rep. 2016; 6:36035. PMC: 5086843. DOI: 10.1038/srep36035. View

Wu M, Zhou F, Cao X, Yang J, Bai Y, Yan X . Abnormal circadian locomotor rhythms and Per gene expression in six-month-old triple transgenic mice model of Alzheimer's disease. Neurosci Lett. 2018; 676:13-18. DOI: 10.1016/j.neulet.2018.04.008. View

Graybeal J, Bozzelli P, Graybeal L, Groeber C, McKnight P, Cox D . Human ApoE ε4 alters circadian rhythm activity, IL-1β, and GFAP in CRND8 mice. J Alzheimers Dis. 2014; 43(3):823-34. DOI: 10.3233/JAD-132009. View

10.

Nakamura T, Nakamura W, Yamazaki S, Kudo T, Cutler T, Colwell C . Age-related decline in circadian output. J Neurosci. 2011; 31(28):10201-5. PMC: 3155746. DOI: 10.1523/JNEUROSCI.0451-11.2011. View

11.

Banks G, Nolan P . Assessment of Circadian and Light-Entrainable Parameters in Mice Using Wheel-Running Activity. Curr Protoc Mouse Biol. 2015; 1(3):369-81. DOI: 10.1002/9780470942390.mo110123. View

12.

Boggs K, Kakalec P, Smith M, Howell S, Flinn J . Circadian wheel running behavior is altered in an APP/E4 mouse model of late onset Alzheimer's disease. Physiol Behav. 2017; 182:137-142. DOI: 10.1016/j.physbeh.2017.09.021. View

13.

McAuley J, Miller J, Beck E, Nagy Z, Pang K . Age-related disruptions in circadian timing: evidence for "split" activity rhythms in the SAMP8. Neurobiol Aging. 2002; 23(4):625-32. DOI: 10.1016/s0197-4580(01)00344-x. View

14.

Bedrosian T, Herring K, Weil Z, Nelson R . Altered temporal patterns of anxiety in aged and amyloid precursor protein (APP) transgenic mice. Proc Natl Acad Sci U S A. 2011; 108(28):11686-91. PMC: 3136261. DOI: 10.1073/pnas.1103098108. View

15.

Musiek E, Bhimasani M, Zangrilli M, Morris J, Holtzman D, Ju Y . Circadian Rest-Activity Pattern Changes in Aging and Preclinical Alzheimer Disease. JAMA Neurol. 2018; 75(5):582-590. PMC: 5885197. DOI: 10.1001/jamaneurol.2017.4719. View

16.

Plucinska K, Crouch B, Koss D, Robinson L, Siebrecht M, Riedel G . Knock-in of human BACE1 cleaves murine APP and reiterates Alzheimer-like phenotypes. J Neurosci. 2014; 34(32):10710-28. PMC: 4122804. DOI: 10.1523/JNEUROSCI.0433-14.2014. View

17.

Ancoli-Israel S, Klauber M, Jones D, Kripke D, Martin J, Mason W . Variations in circadian rhythms of activity, sleep, and light exposure related to dementia in nursing-home patients. Sleep. 1997; 20(1):18-23. View

18.

Navigatore-Fonzo L, Castro A, Pignataro V, Garraza M, Casais M, Anzulovich A . Daily rhythms of cognition-related factors are modified in an experimental model of Alzheimer's disease. Brain Res. 2017; 1660:27-35. DOI: 10.1016/j.brainres.2017.01.033. View

19.

Sundaram S, Nagaraj S, Mahoney H, Portugues A, Li W, Millsaps K . Inhibition of casein kinase 1δ/εimproves cognitive-affective behavior and reduces amyloid load in the APP-PS1 mouse model of Alzheimer's disease. Sci Rep. 2019; 9(1):13743. PMC: 6760153. DOI: 10.1038/s41598-019-50197-x. View

20.

Pardossi-Piquard R, Lauritzen I, Bauer C, Sacco G, Robert P, Checler F . Influence of Genetic Background on Apathy-Like Behavior in Triple Transgenic AD Mice. Curr Alzheimer Res. 2016; 13(8):942-9. DOI: 10.2174/1567205013666160404120106. View