Recurrent Sleep Fragmentation Induces Insulin and Neuroprotective Mechanisms in Middle-Aged Flies

Overview

Journal Front Aging Neurosci

Specialty Geriatrics

Date 2016 Aug 18

PMID 27531979

Citations 10

Authors

Michael J Williams

Emelie Perland

Mikaela M Eriksson

Josef Carlsson

Daniel Erlandsson

Loora Laan

Tabusi Mahebali

Ella Potter

Robert Frediksson

Christian Benedict

Helgi B Schioth

Affiliations

Soon will be listed here.

Abstract

Lack of quality sleep increases central nervous system oxidative stress and impairs removal of neurotoxic soluble metabolites from brain parenchyma. During aging poor sleep quality, caused by sleep fragmentation, increases central nervous system cellular stress. Currently, it is not known how organisms offset age-related cytotoxic metabolite increases in order to safeguard neuronal survival. Furthermore, it is not understood how age and sleep fragmentation interact to affect oxidative stress protection pathways. We demonstrate sleep fragmentation increases systems that protect against oxidative damage and neuroprotective endoplasmic reticulum molecular chaperones, as well as neuronal insulin and dopaminergic expression in middle-aged Drosophila males. Interestingly, even after sleep recovery the expression of these genes was still upregulated in middle-aged flies. Finally, sleep fragmentation generates higher levels of reactive oxygen species (ROS) in middle-aged flies and after sleep recovery these levels remain significantly higher than in young flies. The fact that neuroprotective pathways remain upregulated in middle-aged flies beyond sleep fragmentation suggests it might represent a strong stressor for the brain during later life.

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References

Johnson J, Johnson D, Kraft A, Calkins M, Jakel R, Vargas M . The Nrf2-ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration. Ann N Y Acad Sci. 2008; 1147:61-9. PMC: 2605641. DOI: 10.1196/annals.1427.036. View

Reynolds A, Banks S . Total sleep deprivation, chronic sleep restriction and sleep disruption. Prog Brain Res. 2010; 185:91-103. DOI: 10.1016/B978-0-444-53702-7.00006-3. View

Naidoo N, Casiano V, Cater J, Zimmerman J, Pack A . A role for the molecular chaperone protein BiP/GRP78 in Drosophila sleep homeostasis. Sleep. 2007; 30(5):557-65. DOI: 10.1093/sleep/30.5.557. View

Ramanathan L, Gulyani S, Nienhuis R, Siegel J . Sleep deprivation decreases superoxide dismutase activity in rat hippocampus and brainstem. Neuroreport. 2002; 13(11):1387-90. PMC: 8802885. DOI: 10.1097/00001756-200208070-00007. View

Broughton S, Piper M, Ikeya T, Bass T, Jacobson J, Driege Y . Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proc Natl Acad Sci U S A. 2005; 102(8):3105-10. PMC: 549445. DOI: 10.1073/pnas.0405775102. View

Brown M, Chan M, Zimmerman J, Pack A, Jackson N, Naidoo N . Aging induced endoplasmic reticulum stress alters sleep and sleep homeostasis. Neurobiol Aging. 2014; 35(6):1431-41. PMC: 4019391. DOI: 10.1016/j.neurobiolaging.2013.12.005. View

Nikonova E, Naidoo N, Zhang L, Romer M, Cater J, Scharf M . Changes in components of energy regulation in mouse cortex with increases in wakefulness. Sleep. 2010; 33(7):889-900. PMC: 2894431. DOI: 10.1093/sleep/33.7.889. View

Butovsky O, Koronyo-Hamaoui M, Kunis G, Ophir E, Landa G, Cohen H . Glatiramer acetate fights against Alzheimer's disease by inducing dendritic-like microglia expressing insulin-like growth factor 1. Proc Natl Acad Sci U S A. 2006; 103(31):11784-9. PMC: 1544247. DOI: 10.1073/pnas.0604681103. View

Jing X, Shi H, Zhang C, Ren M, Han M, Wei X . Dimethyl fumarate attenuates 6-OHDA-induced neurotoxicity in SH-SY5Y cells and in animal model of Parkinson's disease by enhancing Nrf2 activity. Neuroscience. 2014; 286:131-40. DOI: 10.1016/j.neuroscience.2014.11.047. View

10.

Cirelli C . Sleep disruption, oxidative stress, and aging: new insights from fruit flies. Proc Natl Acad Sci U S A. 2006; 103(38):13901-2. PMC: 1599884. DOI: 10.1073/pnas.0606652103. View

11.

Koh K, Evans J, Hendricks J, Sehgal A . A Drosophila model for age-associated changes in sleep:wake cycles. Proc Natl Acad Sci U S A. 2006; 103(37):13843-7. PMC: 1564207. DOI: 10.1073/pnas.0605903103. View

12.

Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A . Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002; 3(7):RESEARCH0034. PMC: 126239. DOI: 10.1186/gb-2002-3-7-research0034. View

13.

Ramakers C, Ruijter J, Lekanne Deprez R, Moorman A . Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci Lett. 2003; 339(1):62-6. DOI: 10.1016/s0304-3940(02)01423-4. View

14.

Shaw P, Cirelli C, Greenspan R, Tononi G . Correlates of sleep and waking in Drosophila melanogaster. Science. 2000; 287(5459):1834-7. DOI: 10.1126/science.287.5459.1834. View

15.

Jones T, Brewer G . Age-related deficiencies in complex I endogenous substrate availability and reserve capacity of complex IV in cortical neuron electron transport. Biochim Biophys Acta. 2009; 1797(2):167-76. PMC: 2812684. DOI: 10.1016/j.bbabio.2009.09.009. View

16.

Schrempf W, Brandt M, Storch A, Reichmann H . Sleep disorders in Parkinson's disease. J Parkinsons Dis. 2014; 4(2):211-21. DOI: 10.3233/JPD-130301. View

17.

Gopalakrishnan A, Ji L, Cirelli C . Sleep deprivation and cellular responses to oxidative stress. Sleep. 2004; 27(1):27-35. DOI: 10.1093/sleep/27.1.27. View

18.

Naylor E, Bergmann B, Krauski K, Zee P, Takahashi J, Vitaterna M . The circadian clock mutation alters sleep homeostasis in the mouse. J Neurosci. 2000; 20(21):8138-43. PMC: 6772726. View

19.

Ramalingam M, Kim S . Insulin exerts neuroprotective effects via Akt/Bcl-2 signaling pathways in differentiated SH-SY5Y cells. J Recept Signal Transduct Res. 2014; 35(1):1-7. DOI: 10.3109/10799893.2014.922576. View

20.

Sano R, Reed J . ER stress-induced cell death mechanisms. Biochim Biophys Acta. 2013; 1833(12):3460-3470. PMC: 3834229. DOI: 10.1016/j.bbamcr.2013.06.028. View