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Chronic Sleep Restriction Induces Aβ Accumulation by Disrupting the Balance of Aβ Production and Clearance in Rats

  • Beiyu Zhao
  • Peng Liu
  • Meng Wei
  • Yanbo Li
  • Jie Liu
  • Louyan Ma
  • Suhang Shang
  • Yu Jiang
  • Kang Huo
  • Jin Wang
  • Qiumin Qu
Original Paper
  • 38 Downloads

Abstract

Amyloid-β (Aβ) plays an important role in Alzheimer’s disease (AD) pathogenesis, and growing evidence has shown that poor sleep quality is one of the risk factors for AD, but the mechanisms of sleep deprivation leading to AD have still not been fully demonstrated. In the present study, we used wild-type (WT) rats to determine the effects of chronic sleep restriction (CSR) on Aβ accumulation. We found that CSR-21d rats had learning and memory functional decline in the Morris water maze (MWM) test. Meanwhile, Aβ42 deposition in the hippocampus and the prefrontal cortex was high after a 21-day sleep restriction. Moreover, compared with the control rats, CSR rats had increased expression of β-site APP-cleaving enzyme 1 (BACE1) and sAPPβ and decreased sAPPα levels in both the hippocampus and the prefrontal cortex, and the BACE1 level was positively correlated with the Aβ42 level. Additionally, in CSR-21d rats, low-density lipoprotein receptor-related protein 1 (LRP-1) levels were low, while receptor of advanced glycation end products (RAGE) levels were high in the hippocampus and the prefrontal cortex, and these transporters were significantly correlated with Aβ42 levels. In addition, CSR-21d rats had decreased plasma Aβ42 levels and soluble LRP1 (sLRP1) levels compared with the control rats. Altogether, this study demonstrated that 21 days of CSR could lead to brain Aβ accumulation in WT rats. The underlying mechanisms may be related to increased Aβ production via upregulation of the BACE1 pathway and disrupted Aβ clearance affecting brain and peripheral Aβ transport.

Keywords

Alzheimer’s disease Chronic sleep restriction Amyloid-β accumulation BACE1 LRP-1 RAGE 

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China to Qiumin Qu (No. 81771168).

Compliance with Ethical Standards

Conflict of interest

The authors have no conflicts of interest to disclose.

References

  1. 1.
    Mayeux R, Stern Y (2012) Epidemiology of Alzheimer disease. Cold Spring Harb Perspect Med 2:a011460.  https://doi.org/10.1101/cshperspect.a006239 CrossRefGoogle Scholar
  2. 2.
    Lemere CA, Masliah E (2010) Can Alzheimer disease be prevented by amyloid-beta immunotherapy? Nat Rev Neurol 6:108–119CrossRefGoogle Scholar
  3. 3.
    Holtzman DM, Morris JC, Goate AM (2011) Alzheimer’s disease: the challenge of the second century. Sci Transl Med 3:77 sr71Google Scholar
  4. 4.
    Masters CL, Selkoe DJ (2012) Biochemistry of amyloid beta-protein and amyloid deposits in Alzheimer disease. Cold Spring Harb Perspect Med 2:a006262CrossRefGoogle Scholar
  5. 5.
    Thinakaran G, Koo EH (2008) Amyloid precursor protein trafficking, processing, and function. J Biol Chem 283:29615–29619CrossRefGoogle Scholar
  6. 6.
    Steiner H, Fluhrer R, Haass C (2008) Intramembrane proteolysis by gamma-secretase. J Biol Chem 283:29627–29631CrossRefGoogle Scholar
  7. 7.
    Cai H, Wang Y, McCarthy D, Wen H, Borchelt DR, Price DL, Wong PC (2001) BACE1 is the major beta-secretase for generation of Abeta peptides by neurons. Nat Neurosci 4:233–234CrossRefGoogle Scholar
  8. 8.
    Chasseigneaux S, Allinquant B (2012) Functions of Abeta, sAPPalpha and sAPPbeta: similarities and differences. J Neurochem 120 Suppl 1:99–108CrossRefGoogle Scholar
  9. 9.
    Deane R, Bell RD, Sagare A, Zlokovic BV (2009) Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer’s disease. CNS Neurol Disord Drug Target 8:16–30CrossRefGoogle Scholar
  10. 10.
    Bell RD (2012) The imbalance of vascular molecules in Alzheimer’s disease. J Alzheimer’s Dis 32:699–709CrossRefGoogle Scholar
  11. 11.
    Sagare AP, Deane R, Zlokovic BV (2012) Low-density lipoprotein receptor-related protein 1: a physiological Abeta homeostatic mechanism with multiple therapeutic opportunities. Pharmacol Ther 136:94–105CrossRefGoogle Scholar
  12. 12.
    Cai Z, Liu N, Wang C, Qin B, Zhou Y, Xiao M, Chang L, Yan LJ, Zhao B (2016) Role of RAGE in Alzheimer’s Disease. Cell Mol Neurobiol 36:483–495CrossRefGoogle Scholar
  13. 13.
    Wang P, Huang R, Lu S, Xia W, Cai R, Sun H, Wang S (2016) RAGE and AGEs in mild cognitive impairment of diabetic patients: a cross-sectional study. PloS ONE 11:e0145521CrossRefGoogle Scholar
  14. 14.
    Rogers J, Li R, Mastroeni D, Grover A, Leonard B, Ahern G, Cao P, Kolody H, Vedders L, Kolb WP, Sabbagh M (2006) Peripheral clearance of amyloid beta peptide by complement C3-dependent adherence to erythrocytes. Neurobiol Aging 27:1733–1739CrossRefGoogle Scholar
  15. 15.
    Sparks DL (2007) Cholesterol metabolism and brain amyloidosis: evidence for a role of copper in the clearance of Abeta through the liver. Curr Alzheimer Res 4:165–169CrossRefGoogle Scholar
  16. 16.
    Arvanitakis Z, Lucas JA, Younkin LH, Younkin SG, Graff-Radford NR (2002) Serum creatinine levels correlate with plasma amyloid Beta protein. Alzheimer Dis Assoc Disord 16:187–190CrossRefGoogle Scholar
  17. 17.
    Xiang Y, Bu XL, Liu YH, Zhu C, Shen LL, Jiao SS, Zhu XY, Giunta B, Tan J, Song WH, Zhou HD, Zhou XF, Wang YJ (2015) Physiological amyloid-beta clearance in the periphery and its therapeutic potential for Alzheimer’s disease. Acta Neuropathol 130:487–499CrossRefGoogle Scholar
  18. 18.
    Underwood E (2013) Neuroscience. Sleep: the brain’s housekeeper? Science 342:301CrossRefGoogle Scholar
  19. 19.
    Tabuchi M, Lone SR, Liu S, Liu Q, Zhang J, Spira AP, Wu MN (2015) Sleep interacts with abeta to modulate intrinsic neuronal excitability. Curr Biol 25:702–712CrossRefGoogle Scholar
  20. 20.
    Moran M, Lynch CA, Walsh C, Coen R, Coakley D, Lawlor BA (2005) Sleep disturbance in mild to moderate Alzheimer’s disease. Sleep Med 6:347–352CrossRefGoogle Scholar
  21. 21.
    Liguori C, Nuccetelli M, Izzi F, Sancesario G, Romigi A, Martorana A, Amoroso C, Bernardini S, Marciani MG, Mercuri NB, Placidi F (2016) Rapid eye movement sleep disruption and sleep fragmentation are associated with increased orexin-A cerebrospinal-fluid levels in mild cognitive impairment due to Alzheimer’s disease. Neurobiol Aging 40:120–126CrossRefGoogle Scholar
  22. 22.
    Ju YE, Lucey BP, Holtzman DM (2014) Sleep and Alzheimer disease pathology–a bidirectional relationship. Nat Rev Neurol 10:115–119CrossRefGoogle Scholar
  23. 23.
    Lim AS, Kowgier M, Yu L, Buchman AS, Bennett DA (2013) Sleep Fragmentation and the Risk of Incident Alzheimer’s Disease and Cognitive Decline in Older Persons. Sleep 36:1027–1032CrossRefGoogle Scholar
  24. 24.
    Osorio RS, Pirraglia E, Aguera-Ortiz LF, During EH, Sacks H, Ayappa I, Walsleben J, Mooney A, Hussain A, Glodzik L, Frangione B, Martinez-Martin P, de Leon MJ (2011) Greater risk of Alzheimer’s disease in older adults with insomnia. J Am Geriatr Soc 59:559–562CrossRefGoogle Scholar
  25. 25.
    Wei M, Zhao B, Huo K, Deng Y, Shang S, Liu J, Li Y, Ma L, Jiang Y, Dang L, Chen C, Wei S, Zhang J, Yang H, Gao F, Qu Q (2017) Sleep deprivation induced plasma amyloid-beta transport disturbance in healthy young adults. J Alzheimer’s Dis 57:899–906CrossRefGoogle Scholar
  26. 26.
    Kang JE, Lim MM, Bateman RJ, Lee JJ, Smyth LP, Cirrito JR, Fujiki N, Nishino S, Holtzman DM (2009) Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle. Science 326:1005–1007CrossRefGoogle Scholar
  27. 27.
    Zhao HY, Wu HJ, He JL, Zhuang JH, Liu ZY, Huang LQ, Zhao ZX (2017) Chronic Sleep Restriction Induces Cognitive Deficits and Cortical Beta-Amyloid Deposition in Mice via BACE1-Antisense Activation. CNS Neurosci Ther 23:233–240CrossRefGoogle Scholar
  28. 28.
    Roman V, Hagewoud R, Luiten PG, Meerlo P (2006) Differential effects of chronic partial sleep deprivation and stress on serotonin-1A and muscarinic acetylcholine receptor sensitivity. J Sleep Res 15:386–394CrossRefGoogle Scholar
  29. 29.
    Christie MA, McKenna JT, Connolly NP, McCarley RW, Strecker RE (2008) 24 hours of sleep deprivation in the rat increases sleepiness and decreases vigilance: introduction of the rat-psychomotor vigilance task. J Sleep Res 17:376–384CrossRefGoogle Scholar
  30. 30.
    D’Hooge R, De Deyn PP (2001) Applications of the Morris water maze in the study of learning and memory. Brain Res Brain Res Rev 36:60–90CrossRefGoogle Scholar
  31. 31.
    Czeh B, Abumaria N, Rygula R, Fuchs E (2010) Quantitative changes in hippocampal microvasculature of chronically stressed rats: no effect of fluoxetine treatment. Hippocampus 20:174–185Google Scholar
  32. 32.
    Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O’Donnell J, Christensen DJ, Nicholson C, Iliff JJ, Takano T, Deane R, Nedergaard M (2013) Sleep drives metabolite clearance from the adult brain. Science 342:373–377CrossRefGoogle Scholar
  33. 33.
    Spira AP, Gamaldo AA, An Y, Wu MN, Simonsick EM, Bilgel M, Zhou Y, Wong DF, Ferrucci L, Resnick SM (2013) Self-reported sleep and beta-amyloid deposition in community-dwelling older adults. JAMA Neurol 70:1537–1543Google Scholar
  34. 34.
    Zhang YW, Thompson R, Zhang H, Xu H (2011) APP processing in Alzheimer’s disease. Mol Brain 4:3CrossRefGoogle Scholar
  35. 35.
    Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297:353–356CrossRefGoogle Scholar
  36. 36.
    Dawkins E, Small DH (2014) Insights into the physiological function of the beta-amyloid precursor protein: beyond Alzheimer’s disease. J Neurochem 129:756–769CrossRefGoogle Scholar
  37. 37.
    Kanekiyo T, Bu G (2014) The low-density lipoprotein receptor-related protein 1 and amyloid-beta clearance in Alzheimer’s disease. Front Aging Neurosci 6:93CrossRefGoogle Scholar
  38. 38.
    Waldron E, Heilig C, Schweitzer A, Nadella N, Jaeger S, Martin AM, Weggen S, Brix K, Pietrzik CU (2008) LRP1 modulates APP trafficking along early compartments of the secretory pathway. Neurobiol Dis 31:188–197CrossRefGoogle Scholar
  39. 39.
    Wan W, Chen H, Li Y (2014) The potential mechanisms of Abeta-receptor for advanced glycation end-products interaction disrupting tight junctions of the blood-brain barrier in Alzheimer’s disease. Int J Neurosci 124:75–81CrossRefGoogle Scholar
  40. 40.
    Dickstein DL, Biron KE, Ujiie M, Pfeifer CG, Jeffries AR, Jefferies WA (2006) Abeta peptide immunization restores blood-brain barrier integrity in Alzheimer disease. FASEB J 20:426–433CrossRefGoogle Scholar
  41. 41.
    Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, Jacobs AH, Wyss-Coray T, Vitorica J, Ransohoff RM, Herrup K, Frautschy SA, Finsen B, Brown GC, Verkhratsky A, Yamanaka K, Koistinaho J, Latz E, Halle A, Petzold GC, Town T, Morgan D, Shinohara ML, Perry VH, Holmes C, Bazan NG, Brooks DJ, Hunot S, Joseph B, Deigendesch N, Garaschuk O, Boddeke E, Dinarello CA, Breitner JC, Cole GM, Golenbock DT, Kummer MP (2015) Neuroinflammation in Alzheimer’s disease. Lancet Neurol 14:388–405CrossRefGoogle Scholar
  42. 42.
    Zhao J, O’Connor T, Vassar R (2011) The contribution of activated astrocytes to Abeta production: implications for Alzheimer’s disease pathogenesis. J Neuroinflamm 8:150CrossRefGoogle Scholar
  43. 43.
    Jin P, Kim JA, Choi DY, Lee YJ, Jung HS, Hong JT (2013) Anti-inflammatory and anti-amyloidogenic effects of a small molecule, 2,4-bis(p-hydroxyphenyl)-2-butenal in Tg2576 Alzheimer’s disease mice model. J Neuroinflamm 10:2Google Scholar
  44. 44.
    Jaeger LB, Dohgu S, Sultana R, Lynch JL, Owen JB, Erickson MA, Shah GN, Price TO, Fleegal-Demotta MA, Butterfield DA, Banks WA (2009) Lipopolysaccharide alters the blood-brain barrier transport of amyloid beta protein: a mechanism for inflammation in the progression of Alzheimer’s disease. Brain Behav Immun 23:507–517CrossRefGoogle Scholar
  45. 45.
    Kincheski GC, Valentim IS, Clarke JR, Cozachenco D, Castelo-Branco MTL, Ramos-Lobo AM, Rumjanek V, Donato J Jr, De Felice FG, Ferreira ST (2017) Chronic sleep restriction promotes brain inflammation and synapse loss, and potentiates memory impairment induced by amyloid-beta oligomers in mice. Brain Behav Immun 64:140–151CrossRefGoogle Scholar
  46. 46.
    Shearer WT, Reuben JM, Mullington JM, Price NJ, Lee BN, Smith EO, Szuba MP, Van Dongen HP, Dinges DF (2001) Soluble TNF-alpha receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight. J Allergy Clin Immunol 107:165–170CrossRefGoogle Scholar
  47. 47.
    Roberts KF, Elbert DL, Kasten TP, Patterson BW, Sigurdson WC, Connors RE, Ovod V, Munsell LY, Mawuenyega KG, Miller-Thomas MM, Moran CJ, Cross DT, Derdeyn CP, Bateman RJ (2014) Amyloid-beta efflux from the central nervous system into the plasma. Ann Neurol 76:837–844CrossRefGoogle Scholar
  48. 48.
    Benedict C, Cedernaes J, Giedraitis V, Nilsson EK, Hogenkamp PS, Vagesjo E, Massena S, Pettersson U, Christoffersson G, Phillipson M, Broman JE, Lannfelt L, Zetterberg H, Schioth HB (2014) Acute sleep deprivation increases serum levels of neuron-specific enolase (NSE) and S100 calcium binding protein B (S-100B) in healthy young men. Sleep 37:195–198CrossRefGoogle Scholar
  49. 49.
    Ruskin DN, Dunn KE, Billiot I, Bazan NG, LaHoste GJ (2006) Eliminating the adrenal stress response does not affect sleep deprivation-induced acquisition deficits in the water maze. Life Sci 78:2833–2838CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NeurologyThe First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
  2. 2.Department of NeurologyShaanxi Provincial People’s HospitalXi’anChina

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