Abstract
Cognitive decline, memory impairment and circadian rhythm disturbance are iconic manifestations of Alzheimer’s disease (AD). APPswe/PS1dE9 (APP/PS1) mice, a model of AD, show deficits in multiple learning and memory abilities, synaptic plasticity, and behavioral circadian rhythm, but whether circadian differences in cognitive performance and synaptic plasticity could be affected in AD remain unclear. Here, the cognitive behaviors of 6-month-old APP/PS1 mice were assessed by multiple behavior tests in the rest phase (light period) or active phase (dark period) of the day. The possible electrophysiological mechanism was subsequently investigated by in vivo hippocampal long-term potentiation (LTP) recording, and the locomotor activity rhythm of the mice was detected using wheel-running activities. Compared to wild-type (WT) mice, APP/PS1 mice exhibited long-term spatial memory impairment and in vivo hippocampal LTP suppression. In addition, in APP/PS1 mice, circadian differences in new object recognition memory and LTP were lost, and the circadian difference in long-term spatial memory was decreased, accompanied by a less robust locomotor activity rhythm. These results indicate that the loss of circadian differences in new object recognition memory and the decrease in the circadian difference in long-term spatial memory in APP/PS1 mice, which are closely associated with the loss of the circadian difference in LTP and less robust locomotor activity, might occur early in the course of AD.
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References
Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39. https://doi.org/10.1038/361031a0
Brandeis R, Brandys Y, Yehuda S (1989) The use of the Morris water maze in the study of memory and learning. Int J Neurosci 48:29–69. https://doi.org/10.3109/00207458909002151
Chaudhury D, Colwell CS (2002) Circadian modulation of learning and memory in fear-conditioned mice. Behav Brain Res 133:95–108. https://doi.org/10.1016/S0166-4328(01)00471-5
Chaudhury D, Wang LM, Colwell CS (2005) Circadian regulation of hippocampal long-term potentiation. J Biol Rhythm 20:225–236. https://doi.org/10.1177/0748730405276352
Gaggioni G, Ly JQM, Muto V, Chellappa SL, Jaspar M, Meyer C, Delfosse T, Vanvinckenroye A, Dumont R, Coppieters ‘t Wallant D, Berthomier C, Narbutas J, Van Egroo M, Luxen A, Salmon E, Collette F, Phillips C, Schmidt C, Vandewalle G (2019) Age-related decrease in cortical excitability circadian variations during sleep loss and its links with cognition. Neurobiol Aging 78:52–63. https://doi.org/10.1016/j.neurobiolaging.2019.02.004
Gerstner JR, Yin JC (2010) Circadian rhythms and memory formation. Nat Rev Neurosci 11:577–588. https://doi.org/10.1038/nrn2881
Jia J, Hu J, Huo X, Miao R, Zhang Y, Ma F (2019) Effects of vitamin D supplementation on cognitive function and blood Abeta-related biomarkers in older adults with Alzheimer’s disease: a randomised, double-blind, placebo-controlled trial. J Neurol Neurosurg Psychiatry. https://doi.org/10.1136/jnnp-2018-320199
Jilg A, Bechstein P, Saade A, Dick M, Li TX, Tosini G, Rami A, Zemmar A, Stehle JH (2019) Melatonin modulates daytime-dependent synaptic plasticity and learning efficiency. J Pineal Res 66:e12553. https://doi.org/10.1111/jpi.12553
Krishnan HC, Lyons LC (2015) Synchrony and desynchrony in circadian clocks: impacts on learning and memory. Learn Mem 22:426–437. https://doi.org/10.1101/lm.038877.115
Lane CA, Hardy J, Schott JM (2018) Alzheimer’s disease. Eur J Neurol 25:59–70. https://doi.org/10.1111/ene.13439
Li T, Jiao JJ, Holscher C, Wu MN, Zhang J, Tong JQ, Dong XF, Qu XS, Cao Y, Cai HY, Su Q, Qi JS (2018) A novel GLP-1/GIP/Gcg triagonist reduces cognitive deficits and pathology in the 3xTg mouse model of Alzheimer’s disease. Hippocampus 28:358–372. https://doi.org/10.1002/hipo.22837
Macedo AC, Balouch S, Tabet N (2017) Is sleep disruption a risk factor for Alzheimer’s disease? J Alzheimers Dis 58:993–1002. https://doi.org/10.3233/JAD-161287
Musiek ES, Xiong DD, Holtzman DM (2015) Sleep, circadian rhythms, and the pathogenesis of Alzheimer disease. Exp Mol Med 47:e148. https://doi.org/10.1038/emm.2014.121
Nishikawa Y, Shibata S, Watanabe S (1995) Circadian changes in long-term potentiation of rat suprachiasmatic field potentials elicited by optic nerve stimulation in vitro. Brain Res 695:158–162. https://doi.org/10.1016/0006-8993(95)00717-5
O'Neal-Moffitt G, Pilli J, Kumar SS, Olcese J (2014) Genetic deletion of MT(1)/MT(2) melatonin receptors enhances murine cognitive and motor performance. Neuroscience 277:506–521. https://doi.org/10.1016/j.neuroscience.2014.07.018
Oyegbami O, Collins HM, Pardon MC, Ebling FJP, Heery DM, Moran PM (2017) Abnormal clock gene expression and Locomotor activity rhythms in two month-old female APPSwe/PS1dE9 mice. Curr Alzheimer Res 14:850–860. https://doi.org/10.2174/1567205014666170317113159
Patterson C (2018) World Alzheimer report 2018 the state of the art of dementia research: new frontiers. Alzheimer’s Disease International
Reppert SM, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418:935–941. https://doi.org/10.1038/nature00965
Schmid S, Jungwirth B, Gehlert V, Blobner M, Schneider G, Kratzer S, Kellermann K, Rammes G (2017) Intracerebroventricular injection of beta-amyloid in mice is associated with long-term cognitive impairment in the modified hole-board test. Behav Brain Res 324:15–20. https://doi.org/10.1016/j.bbr.2017.02.007
Shi H, Yuan L, Zhang J, Qu XS, Jiao JJ, Qi JS, Wu MN (2016) The Behavioral and pathological characteristics in APPswe/PS1dE9 double-transgenic mouse model of Alzheimer's disease. Chinese Journal of Neuroanatomy 32:499–506. https://doi.org/10.16557/j.cnki.1000-7547.2016.04.014
Sierksma AS, van den Hove DL, Pfau F, Philippens M, Bruno O, Fedele E, Ricciarelli R, Steinbusch HW, Vanmierlo T, Prickaerts J (2014) Improvement of spatial memory function in APPswe/PS1dE9 mice after chronic inhibition of phosphodiesterase type 4D. Neuropharmacology 77:120–130. https://doi.org/10.1016/j.neuropharm.2013.09.015
Stover KR, Campbell MA, Van Winssen CM, Brown RE (2015) Early detection of cognitive deficits in the 3xTg-AD mouse model of Alzheimer’s disease. Behav Brain Res 289:29–38. https://doi.org/10.1016/j.bbr.2015.04.012
Stranahan AM (2012) Chronobiological approaches to Alzheimer’s disease. Curr Alzheimer Res 9:93–98. https://doi.org/10.2174/156720512799015028
Valentinuzzi VS, Menna-Barreto L, Xavier GF (2004) Effect of circadian phase on performance of rats in the Morris water maze task. J Biol Rhythm 19:312–324. https://doi.org/10.1177/0748730404265688
Viana da Silva S, Zhang P, Haberl MG, Labrousse V, Grosjean N, Blanchet C, Frick A, Mulle C (2019) Hippocampal mossy Fibers synapses in CA3 pyramidal cells are altered at an early stage in a mouse model of Alzheimer’s disease. J Neurosci 39:4193–4205. https://doi.org/10.1523/JNEUROSCI.2868-18.2019
Wang X, Miao Y, Abulizi J, Li F, Mo Y, Xue W, Li Z (2016) Improvement of Electroacupuncture on APP/PS1 transgenic mice in spatial learning and memory probably due to expression of Abeta and LRP1 in Hippocampus. Evid Based Complement Alternat Med 2016:7603975. https://doi.org/10.1155/2016/7603975
Webster SJ, Bachstetter AD, Van Eldik LJ (2013) Comprehensive behavioral characterization of an APP/PS-1 double knock-in mouse model of Alzheimer’s disease. Alzheimers Res Ther 5:28. https://doi.org/10.1186/alzrt182
Webster SJ, Bachstetter AD, Nelson PT, Schmitt FA, Van Eldik LJ (2014) Using mice to model Alzheimer’s dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models. Front Genet 5:88. https://doi.org/10.3389/fgene.2014.00088
Woo JA, Zhao X, Khan H, Penn C, Wang X, Joly-Amado A, Weeber E, Morgan D, Kang DE (2015) Slingshot-Cofilin activation mediates mitochondrial and synaptic dysfunction via Abeta ligation to beta1-integrin conformers. Cell Death Differ 22:921–934. https://doi.org/10.1038/cdd.2015.5
Wright KP, Lowry CA, Lebourgeois MK (2012) Circadian and wakefulness-sleep modulation of cognition in humans. Front Mol Neurosci 5:50. https://doi.org/10.3389/fnmol.2012.00050
Wu M, Shi H, He Y, Yuan L, Qu X, Zhang J, Wang Z, Cai H, Qi J (2017) Colivelin ameliorates impairments in cognitive behaviors and synaptic plasticity in APP/PS1 transgenic mice. J Alzheimers Dis 59:1067–1078. https://doi.org/10.3233/JAD-170307
Wu M, Zhou F, Cao X, Yang J, Bai Y, Yan X, Cao J, Qi J (2018) Abnormal circadian locomotor rhythms and per gene expression in six-month-old triple transgenic mice model of Alzheimer’s disease. Neurosci Lett 676:13–18. https://doi.org/10.1016/j.neulet.2018.04.008
Zhang Z, Wang HJ, Wang DR, Qu WM, Huang ZL (2017) Red light at intensities above 10 lx alters sleep-wake behavior in mice. Light Sci Appl 6:e16231. https://doi.org/10.1038/lsa.2016.231
Acknowledgments
This work was supported by Fund Program for “Sanjin Scholars” of Shanxi Province, Shanxi Province Science Foundation for Excellent Young Scholars (No. 201801D211005) and Key Research and Development Program (No. 201903D321191), Fund for Shanxi Key Subjects Construction (FSKSC), Fund for Shanxi “1331 Project” Key Subjects Construction (No. XK201708).
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He, Y., Li, Y., Zhou, F. et al. Decreased circadian fluctuation in cognitive behaviors and synaptic plasticity in APP/PS1 transgenic mice. Metab Brain Dis 35, 343–352 (2020). https://doi.org/10.1007/s11011-019-00531-z
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DOI: https://doi.org/10.1007/s11011-019-00531-z