Skip to main content
Log in

Regulation of Sleep Behavior by Overexpression of Amyloid Precursor Protein in Drosophila Neurons

  • Published:
Journal of Shanghai Jiaotong University (Science) Aims and scope Submit manuscript

Abstract

Amyloid precursor protein (APP) can generate neurotoxic β-amyloid 42 (Aβ42) by proteolytic process, which plays a crucial role in the pathogenesis of Alzheimer’s disease (AD). Individuals with mild to moderate AD exhibit sleep disturbance, even before the onset of AD. The purpose of this study is to verify the effect of APP on sleep behavior by using an APP overexpressing Drosophila AD model. APP-overexpressed flies were grouped by age, and their sleep amounts were monitored. Our results demonstrated that APP overexpression had no impacts on sleep amounts in young (4–7 days after eclosion, 4–7AE) flies. However, APP overexpression contributed to lower day and total sleep amounts in the middle-aged (11–14AE) flies. Moreover, old-aged (40AE) flies with overexpressing APP exhibited increased number of sleep bouts and decreased sleep time, indicating sleep fragmentation in these flies. Our results indicated that overexpression of APP in neurons has distinct effects on sleep behavior at different ages, but the specific mechanisms underlying the sleep regulation by APP are needed for further study. In addition, our data also suggest that sleep disturbance in AD animals can be caused by APP expression alterations, which provide a potential treating target for sleep intervention and therapy for AD patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. WYSS-CORAY T. Ageing, neurodegeneration and brain rejuvenation [J]. Nature, 2016, 539(7628): 180–186.

    Article  Google Scholar 

  2. CANTER R G, PENNEY J, TSAI L H. The road to restoring neural circuits for the treatment of Alzheimer’s disease [J]. Nature, 2016, 539(7628): 187–196.

    Article  Google Scholar 

  3. FARCA LUNA A J, PERIER M, SEUGNET L. Amyloid precursor protein in Drosophila glia regulates sleep and genes involved in glutamate recycling [J]. The Journal of Neuroscience, 2017, 37(16): 4289–4300.

    Article  Google Scholar 

  4. ZHUANG L M, PENG F, HUANG Y Y, et al. CHIP modulates APP-induced autophagy-dependent pathological symptoms in Drosophila [J]. Aging Cell, 2020, 19(2): e13070.

    Article  Google Scholar 

  5. CHEN K P, LU H X, GAO T L, et al. Synergic interaction between amyloid precursor protein and neural cell adhesion molecule promotes neurite outgrowth [J]. Oncotarget, 2016, 7(12): 14199–14206.

    Article  Google Scholar 

  6. MOE K E, VITIELLO M V, LARSEN L H, et al. Sleep/wake patterns in Alzheimer’s disease: Relationships with cognition and function [J]. Journal of Sleep Research, 1995, 4(1): 15–20.

    Article  Google Scholar 

  7. SONG Q, PING Y. Aβ42 differently regulates aggression and courtship behaviors in Drosophila [J]. Journal of Fuzhou University (Natural Science Edition), 2017, 45(2): 296–300 (in Chinese).

    Google Scholar 

  8. FENG G, PANG J, YI X, et al. Down-regulation of KV4 channel in Drosophila mushroom body neurons contributes to Aβ42-induced courtship memory deficits [J]. Neuroscience, 2018, 370: 236–245.

    Article  Google Scholar 

  9. JU Y E S, LUCEY B P, HOLTZMAN D M. Sleep and Alzheimer disease pathology: A bidirectional relationship [J]. Nature Reviews Neurology, 2014, 10(2): 115–119.

    Article  Google Scholar 

  10. POLLAK C P, PERLICK D. Sleep problems and institutionalization of the elderly [J]. Journal of Geriatric Psychiatry and Neurology, 1991, 4(4): 204–210.

    Google Scholar 

  11. VITIELLO M V, BORSON S. Sleep disturbances in patients with Alzheimer’s disease: Epidemiology, pathophysiology and treatment [J]. CNS Drugs, 2001, 15(10): 777–796.

    Article  Google Scholar 

  12. MCCURRY S M, ANCOLI-ISRAEL S. Sleep dysfunction in Alzheimer’s disease and other dementias [J]. Current Treatment Options in Neurology, 2003, 5(3): 261–272.

    Article  Google Scholar 

  13. BLIWISE D L. Sleep disorders in Alzheimer’s disease and other dementias [J]. Clinical Cornerstone, 2004, 6(Sup 1A): S16–S28.

    Article  Google Scholar 

  14. SONG Q, FENG G, HUANG Z H, et al. Aberrant axonal arborization of PDF neurons induced by Aβ42-mediated JNK activation underlies sleep disturbance in an Alzheimer’s model [J]. Molecular Neurobiology, 2017, 54(8): 6317–6328.

    Article  Google Scholar 

  15. GUREVICIUS K, LIPPONEN A, TANILA H. Increased cortical and thalamic excitability in freely moving APPswe/PS1dE9 mice modeling epileptic activity associated with Alzheimer’s disease [J]. Cerebral Cortex, 2013, 23(5): 1148–1158.

    Article  Google Scholar 

  16. JIN N X, LIPPONEN A, KOIVISTO H, et al. Increased cortical beta power and spike-wave discharges in middle-aged APP/PS1 mice [J]. Neurobiology of Aging, 2018, 71: 127–141.

    Article  Google Scholar 

  17. DUBOWY C, SEHGAL A. Circadian rhythms and sleep in Drosophila melanogaster [J]. Genetics, 2017, 205(4): 1373–1397.

    Article  Google Scholar 

  18. PITMAN J L, MCGILL J J, KEEGAN K P, et al. A dynamic role for the mushroom bodies in promoting sleep in Drosophila [J]. Nature, 2006, 441(7094): 753–756.

    Article  Google Scholar 

  19. JOINER W J, CROCKER A, WHITE B H, et al. Sleep in Drosophila is regulated by adult mushroom bodies [J]. Nature, 2006, 441(7094): 757–760.

    Article  Google Scholar 

  20. MORAN M, LYNCH C A, WALSH C, et al. Sleep disturbance in mild to moderate Alzheimer’s disease [J]. Sleep Medicine, 2005, 6(4): 347–352.

    Article  Google Scholar 

  21. HAZRA A, CORBETT B F, YOU J C, et al. Corticothalamic network dysfunction and behavioral deficits in a mouse model of Alzheimer’s disease [J]. Neurobiology of Aging, 2016, 44: 96–107.

    Article  Google Scholar 

  22. ZHANG J, PING Y. Regulation of lifespan by jet gene and jet lag in Drosophila [J]. Journal of Fudan University (Natural Science), 2019, 58(2): 199–209 (in Chinese).

    Google Scholar 

  23. BUHL E, HIGHAM J P, HODGE J J L. Alzheimer’s disease-associated tau alters Drosophila circadian activity, sleep and clock neuron electrophysiology [J]. Neurobiology of Disease, 2019, 130: 104507.

    Article  Google Scholar 

  24. FERNANDEZ-FUNEZ P, DE MENA L, RINCONLIMAS D E. Modeling the complex pathology of Alzheimer’s disease in Drosophila [J]. Experimental Neurology, 2015, 274: 58–71.

    Article  Google Scholar 

  25. FENG G, ZHANG J, LI M Z, et al. Control of sleep onset by Shal/Kv4 channels in Drosophila circadian neurons [J]. The Journal of Neuroscience, 2018, 38(42): 9059–9071.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yong Ping  (平勇).

Additional information

Foundation item

the National Natural Science Foundation of China (No. 81970999), and the Shanghai Rising Star Project (No. 19QA1404900)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, M., Ping, Y. Regulation of Sleep Behavior by Overexpression of Amyloid Precursor Protein in Drosophila Neurons. J. Shanghai Jiaotong Univ. (Sci.) 26, 63–68 (2021). https://doi.org/10.1007/s12204-021-2261-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12204-021-2261-0

Key words

CLC number

Document code

Navigation