Abstract
Chronic sleep deprivation (SD) is an overwhelming problem in young students. Firstly, we investigated whether different levels of pre-training SD had effects on spatial performance in adolescent rats. Rats were subjected to 2 or 4 h/day SD for 15 consecutive days. Morris water maze tests were conducted immediately after SD on experimental days 9–15. During the last 3 trials on the first training day, compared with their respective control animals, the rats with prior 4 h SD, but not 2 h SD, showed a significant reduction in percentage of the trials landing the platform without guidance (landing rate). During the whole 6 training days, the rats subjected to 4 h SD, not 2 h SD, spent longer time to locate the platform than the control rats did. In the probe test, the rats with 4 h SD and 2 h SD showed no significant difference with their respective control in time spent in the target quadrant and numbers of platform crossings. These results indicated that chronic prior 4 h SD, but not 2 h SD, impaired spatial acquisition capability in adolescent rats. Secondly, we explored whether huperzine A (Hup A), which has been proved to improve cognitive impairment in dementia, could prevent adolescent rats from chronic 4 h SD-induced learning decline. Hup A (0.1 mg/kg/day) was administered by gavage 30 min before the end of 4 h SD. With hup A treatment, the reduced landing rate was increased and the prolonged escape latency and distance were shortened, which suggested that hup A was promising in preventing the spatial cognitive deficits induced by repeated sleep restriction in adolescents.
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References
Schonauer M, Pawlizki A, Kock C, Gais S. Exploring the effect of sleep and reduced interference on different forms of declarative memory. Sleep. 2014;37(12):1995–2007.
Esposito MJ, Occhionero M, Cicogna P. Sleep deprivation and time-based prospective memory. Sleep. 2015;38(11):1823–6.
Louca M, Short MA. The effect of one night’s sleep deprivation on adolescent neurobehavioral performance. Sleep. 2014;37(11):1799–807.
Scullin MK, Bliwise DL. Sleep, cognition, and normal aging: integrating a half century of multidisciplinary research. Perspect Psychol Sci. 2015;10(1):97–137.
Loessl B, Valerius G, Kopasz M, Hornyak M, Riemann D, Voderholzer U. Are adolescents chronically sleep-deprived? An investigation of sleep habits of adolescents in the Southwest of Germany. Child Care Health Dev (Multicenter Study Research Support, Non-U.S. Gov’t). 2008;34(5):549–56.
Moore M. Behavioral sleep problems in children and adolescents. J Clin Psychol Med Settings. 2012;19(1):77–83.
Mednick SC, Cai DJ, Shuman T, Anagnostaras S, Wixted JT. An opportunistic theory of cellular and systems consolidation. Trends Neurosci (Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t). 2011;34(10):504–14.
Tononi G, Cirelli C. Sleep and the price of plasticity: from synaptic and cellular homeostasis to memory consolidation and integration. Neuron. 2014;81(1):12–34.
Hagewoud R, Havekes R, Novati A, Keijser JN, Van der Zee EA, Meerlo P. Sleep deprivation impairs spatial working memory and reduces hippocampal AMPA receptor phosphorylation. J Sleep Res (Research Support, Non-U.S. Gov’t). 2010;19(2):280–8.
Yoo SS, Hu PT, Gujar N, Jolesz FA, Walker MP. A deficit in the ability to form new human memories without sleep. Nat Neurosci (Comparative Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t). 2007;10(3):385–92.
Van Der Werf YD, Altena E, Schoonheim MM, Sanz-Arigita EJ, Vis JC, De Rijke W, et al. Sleep benefits subsequent hippocampal functioning. Nat Neurosci (Research Support, Non-U.S. Gov’t). 2009;12(2):122–3.
Kirszenblat L, van Swinderen B. The Yin and Yang of sleep and attention. Trends Neurosci. 2015;38(12):776–86.
Kalonia H, Bishnoi M, Kumar A. Possible mechanism involved in sleep deprivation-induced memory dysfunction. Methods Find Exp Clin Pharmacol. 2008;30(7):529–35.
Bowers MB Jr, Hartmann EL, Freedman DX. Sleep deprivation and brain acetylcholine. Science. 1966;153(3742):1416–7.
**ng SH, Zhu CX, Zhang R, An L. Huperzine a in the treatment of Alzheimer’s disease and vascular dementia: a meta-analysis. Evid Based Complement Altern Med. 2014;2014:363985.
Damar U, Gersner R, Johnstone JT, Schachter S, Rotenberg A. Huperzine A as a neuroprotective and antiepileptic drug: a review of preclinical research. Expert Rev Neurother. 2016;16(6):671–80.
Zheng W, **ang YQ, Li XB, Ungvari GS, Chiu HF, Sun F, et al. Adjunctive huperzine A for cognitive deficits in schizophrenia: a systematic review and meta-analysis. Hum Psychopharmacol. 2016;31(4):286–95.
Yang SR, Sun H, Huang ZL, Yao MH, Qu WM. Repeated sleep restriction in adolescent rats altered sleep patterns and impaired spatial learning/memory ability. Sleep (Research Support, Non-U.S. Gov’t). 2012;35(6):849–59.
Spear LP. The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev. 2000;24(4):417–63.
Wang J, Zhang HY, Tang XC. Huperzine a improves chronic inflammation and cognitive decline in rats with cerebral hypoperfusion. J Neurosci Res (Research Support, Non-U.S. Gov’t). 2010;88(4):807–15.
Tobler I, Deboer T, Fischer M. Sleep and sleep regulation in normal and prion protein-deficient mice. J Neurosci (Research Support, Non-U.S. Gov’t). 1997;17(5):1869–79.
Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc. 2006;1(2):848–58.
Qureshi AI, Giles WH, Croft JB, Bliwise DL. Habitual sleep patterns and risk for stroke and coronary heart disease: a 10-year follow-up from NHANES I. Neurology. 1997;48(4):904–11.
Luyster FS, Strollo PJ Jr, Zee PC, Walsh JK. Boards of Directors of the American Academy of Sleep M, the Sleep Research S. Sleep: a health imperative. Sleep. 2012;35(6):727–34.
Novati A, Hulshof HJ, Koolhaas JM, Lucassen PJ, Meerlo P. Chronic sleep restriction causes a decrease in hippocampal volume in adolescent rats, which is not explained by changes in glucocorticoid levels or neurogenesis. Neuroscience (Research Support, Non-U.S. Gov’t). 2011;8(190):145–55.
Soto-Rodriguez S, Lopez-Armas G, Luquin S, Ramos-Zuniga R, Jauregui-Huerta F, Gonzalez-Perez O, et al. Rapid eye movement sleep deprivation produces long-term detrimental effects in spatial memory and modifies the cellular composition of the subgranular zone. Front Cell Neurosci. 2016;10(132):1–13.
Tartar JL, Ward CP, McKenna JT, Thakkar M, Arrigoni E, McCarley RW, et al. Hippocampal synaptic plasticity and spatial learning are impaired in a rat model of sleep fragmentation. Eur J Neurosci (Research Support, N.I.H., Extramural Research Support, U.S. Gov’t, Non-P.H.S.). 2006;23(10):2739–48.
Guan Z, Peng X, Fang J. Sleep deprivation impairs spatial memory and decreases extracellular signal-regulated kinase phosphorylation in the hippocampus. Brain Res (Research Support, U.S. Gov’t, P.H.S.). 2004;1018(1):38–47.
Ward CP, McCoy JG, McKenna JT, Connolly NP, McCarley RW, Strecker RE. Spatial learning and memory deficits following exposure to 24 h of sleep fragmentation or intermittent hypoxia in a rat model of obstructive sleep apnea. Brain Res. 2009;19(1294):128–37.
D’Hooge R, De Deyn PP. Applications of the Morris water maze in the study of learning and memory. Brain Res Brain Res Rev. 2001;36(1):60–90.
Ohba T, Yoshino Y, Ishisaka M, Abe N, Tsuruma K, Shimazawa M, et al. Japanese Huperzia serrata extract and the constituent, huperzine A, ameliorate the scopolamine-induced cognitive impairment in mice. Biosci Biotechnol Biochem. 2015;79(11):1838–44.
Mao XY, Cao DF, Li X, Yin JY, Wang ZB, Zhang Y, et al. Huperzine A ameliorates cognitive deficits in streptozotocin-induced diabetic rats. Int J Mol Sci. 2014;15(5):7667–83.
Tang LL, Wang R, Tang XC. Huperzine A protects SHSY5Y neuroblastoma cells against oxidative stress damage via nerve growth factor production. Eur J Pharmacol. 2005;519(1–2):9–15.
Acknowledgments
We are grateful to students of Shanghai Medical College of Fudan University **ang-Da Meng, Zheng-Liang Li, **ao-** Malin, Wan-Na Chen, Ren-Jie Wang, Jie Chen, Bu-Qing Liang, Yin Wang, and Lin Lin for their contributions to the experimental work. We thank professor Zhi-Li Huang, Department of Pharmacology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University for his critical comments.
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Author Su-Rong Yang declares that she has no conflict of interest. Author Huan-**n Sun declares that she has no conflict of interest. Author Zhen-zhen Hu declares that she has no conflict of interest. Author Si-Heng Wang declares that he has no conflict of interest. Author Hui Sun declares that she has no conflict of interest. Author Yin-Jia Xue declares that he has no conflict of interest. Author Chen-Bo Ye declares that he has no conflict of interest.
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This was not an industry supported study. None of the authors has any financial interest or conflicts of interest related to this work.
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Experimental protocols were approved by the Shanghai Medical Experimental Animal Administrative Committee.
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This study was supported by National Natural Science Foundation of China (81571296), Shanghai Committee of Science and Technology (11ZR1402000), and Shanghai Leading Academic Discipline Project (B119).
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S.-R. Yang, H.-X. Sun, and Z.-Z. Hu contributed equally to this work.
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Yang, SR., Sun, HX., Hu, ZZ. et al. Repeated pre-training sleep restriction in adolescent rats impaired spatial performance. Sleep Biol. Rhythms 15, 57–65 (2017). https://doi.org/10.1007/s41105-016-0080-8
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DOI: https://doi.org/10.1007/s41105-016-0080-8