Molecular Neurobiology

, Volume 53, Issue 5, pp 3439–3447 | Cite as

Chronic Melatonin Treatment Prevents Memory Impairment Induced by Chronic Sleep Deprivation

  • Karem H. AlzoubiEmail author
  • Fadia A. Mayyas
  • Omar F. Khabour
  • Fatima M. Bani Salama
  • Farah H. Alhashimi
  • Nizar M. Mhaidat


Sleep deprivation (SD) has been associated with memory impairment through induction of oxidative stress. Melatonin, which promotes the metabolism of many reactive oxygen species (ROS), has antioxidant and neuroprotective properties. In this study, the effect of melatonin on memory impairment induced by 4 weeks of SD was investigated using rat animal model. Animals were sleep deprived using modified multiple platform model. Melatonin was administered via oral gavage (100 mg/kg/day). Spatial learning and memory were assessed using the radial arm water maze (RAWM). Changes in oxidative stress biomarkers in the hippocampus following treatments were measured using ELISA procedure. The result revealed that SD impaired both short- and long-term memory (P < 0.05). Use of melatonin prevented memory impairment induced by SD. Furthermore, melatonin normalized SD-induced reduction in the hippocampus activity of catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD). In addition, melatonin enhanced the ratio of reduced to oxidized glutathione GSH/GSSG in sleep-deprived rats (P < 0.05) without affecting thiobarbituric acid reactive substance (TBARS) levels (P > 0.05). In conclusion, SD induced memory impairment, which was prevented by melatonin. This was correlated with normalizing hippocampus antioxidant mechanisms during chronic SD.


Melatonin Sleep deprivation Memory Hippocampus Maze 



This project was supported by a grant (224/2013) from Deanship of Research at the Jordan University of Science and Technology.

Financial Support

Grant number: 224/2013, from Deanship of Research at the Jordan University of Science and Technology.


  1. 1.
    Greene R, Siegel J (2004) Sleep: a functional enigma. Neuromolecular Med 5(1):59–68. doi: 10.1385/NMM:5:1:059 CrossRefPubMedGoogle Scholar
  2. 2.
    Ohlmann KK, O’Sullivan MI (2009) The costs of short sleep. AAOHN J 57(9):381–385. doi: 10.3928/08910162-20090817-02, quiz 386–387 CrossRefPubMedGoogle Scholar
  3. 3.
    Gyton C, Hall E (2006) States of brain activity-sleep, brain waves, epilepsy, phycosis sleep. In: Medical Physiology. Elsivier Ins., Philadelphia, PA, pp. 739–741Google Scholar
  4. 4.
    Silber MH, Ancoli-Israel S, Bonnet MH, Chokroverty S, Grigg-Damberger MM, Hirshkowitz M, Kapen S, Keenan SA et al (2007) The visual scoring of sleep in adults. J Clin Sleep Med 3(2):121–131PubMedGoogle Scholar
  5. 5.
    Singh R, Kiloung J, Singh S, Sharma D (2008) Effect of paradoxical sleep deprivation on oxidative stress parameters in brain regions of adult and old rats. Biogerontology 9(3):153–162. doi: 10.1007/s10522-008-9124-z CrossRefPubMedGoogle Scholar
  6. 6.
    Zagaar M, Alhaider I, Dao A, Levine A, Alkarawi A, Alzubaidy M, Alkadhi K (2012) The beneficial effects of regular exercise on cognition in REM sleep deprivation: behavioral, electrophysiological and molecular evidence. Neurobiol Dis 45(3):1153–1162. doi: 10.1016/j.nbd.2011.12.039 CrossRefPubMedGoogle Scholar
  7. 7.
    Alhaider IA, Aleisa AM, Tran TT, Alzoubi KH, Alkadhi KA (2010) Chronic caffeine treatment prevents sleep deprivation-induced impairment of cognitive function and synaptic plasticity. Sleep 33(4):437–444CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Aleisa AM, Alzoubi KH, Alkadhi KA (2011) Post-learning REM sleep deprivation impairs long-term memory: reversal by acute nicotine treatment. Neurosci Lett 499(1):28–31. doi: 10.1016/j.neulet.2011.05.025 CrossRefPubMedGoogle Scholar
  9. 9.
    Smith C, Kelly G (1988) Paradoxical sleep deprivation applied two days after end of training retards learning. Physiol Behav 43(2):213–216CrossRefPubMedGoogle Scholar
  10. 10.
    Aleisa AM, Helal G, Alhaider IA, Alzoubi KH, Srivareerat M, Tran TT, Al-Rejaie SS, Alkadhi KA (2011) Acute nicotine treatment prevents REM sleep deprivation-induced learning and memory impairment in rat. Hippocampus 21(8):899–909. doi: 10.1002/hipo.20806 PubMedGoogle Scholar
  11. 11.
    Mhaidat NM, Alzoubi KH, Khabour OF, Tashtoush NH, Banihani SA, Abdul-Razzak KK (2015) Exploring the effect of vitamin C on sleep deprivation induced memory impairment. Brain Res Bull 113:41–47. doi: 10.1016/j.brainresbull.2015.02.002 CrossRefPubMedGoogle Scholar
  12. 12.
    Jiang F, Shen XM, Li SH, Cui ML, Zhang Y, Wang C, Yu XG, Yan CH (2009) Effects of chronic partial sleep deprivation on growth and learning/memory in young rats. Zhongguo Dang Dai Er Ke Za Zhi 11(2):128–132PubMedGoogle Scholar
  13. 13.
    Alzoubi KH, Khabour OF, Salah HA, Hasan Z (2013) Vitamin E prevents high-fat high-carbohydrates diet-induced memory impairment: the role of oxidative stress. Physiol Behav 119:72–78. doi: 10.1016/j.physbeh.2013.06.011 CrossRefPubMedGoogle Scholar
  14. 14.
    Alzoubi KH, Khabour OF, Tashtoush NH, Al-Azzam SI, Mhaidat NM (2013) Evaluation of the effect of pentoxifylline on sleep-deprivation induced memory impairment. Hippocampus 23(9):812–819. doi: 10.1002/hipo.22135 CrossRefPubMedGoogle Scholar
  15. 15.
    Alzoubi KH, Khabour OF, Salah HA, Abu Rashid BE (2013) The combined effect of sleep deprivation and Western diet on spatial learning and memory: role of BDNF and oxidative stress. J Mol Neurosci 50(1):124–133. doi: 10.1007/s12031-012-9881-7 CrossRefPubMedGoogle Scholar
  16. 16.
    Alzoubi KH, Khabour OF, Rashid BA, Damaj IM, Salah HA (2012) The neuroprotective effect of vitamin E on chronic sleep deprivation-induced memory impairment: the role of oxidative stress. Behav Brain Res 226(1):205–210. doi: 10.1016/j.bbr.2011.09.017 CrossRefPubMedGoogle Scholar
  17. 17.
    Alhaider IA, Aleisa AM, Tran TT, Alkadhi KA (2010) Caffeine prevents sleep loss-induced deficits in long-term potentiation and related signaling molecules in the dentate gyrus. Eur J Neurosci 31(8):1368–1376. doi: 10.1111/j.1460-9568.2010.07175.x CrossRefPubMedGoogle Scholar
  18. 18.
    Izquierdo I, Bevilaqua LR, Rossato JI, da Silva WC, Bonini J, Medina JH, Cammarota M (2008) The molecular cascades of long-term potentiation underlie memory consolidation of one-trial avoidance in the CA1 region of the dorsal hippocampus, but not in the basolateral amygdala or the neocortex. Neurotox Res 14(2–3):273–294CrossRefPubMedGoogle Scholar
  19. 19.
    McDermott CM, Hardy MN, Bazan NG, Magee JC (2006) Sleep deprivation-induced alterations in excitatory synaptic transmission in the CA1 region of the rat hippocampus. J Physiol 570(Pt 3):553–565. doi: 10.1113/jphysiol.2005.093781 CrossRefPubMedGoogle Scholar
  20. 20.
    Ramanathan L, Gulyani S, Nienhuis R, Siegel JM (2002) Sleep deprivation decreases superoxide dismutase activity in rat hippocampus and brainstem. Neuroreport 13(11):1387–1390CrossRefPubMedGoogle Scholar
  21. 21.
    Reimund E (1994) The free radical flux theory of sleep. Med Hypotheses 43(4):231–233CrossRefPubMedGoogle Scholar
  22. 22.
    Silva RH, Abilio VC, Takatsu AL, Kameda SR, Grassl C, Chehin AB, Medrano WA, Calzavara MB et al (2004) Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice. Neuropharmacology 46(6):895–903. doi: 10.1016/j.neuropharm.2003.11.032 CrossRefPubMedGoogle Scholar
  23. 23.
    Reiter RJ, Tamura H, Tan DX, Xu XY (2014) Melatonin and the circadian system: contributions to successful female reproduction. Fertil Steril 102(2):321–328. doi: 10.1016/j.fertnstert.2014.06.014 CrossRefPubMedGoogle Scholar
  24. 24.
    Zhdanova IV, Wurtman RJ, Balcioglu A, Kartashov AI, Lynch HJ (1998) Endogenous melatonin levels and the fate of exogenous melatonin: age effects. J Gerontol A Biol Sci Med Sci 53(4):B293–B298CrossRefPubMedGoogle Scholar
  25. 25.
    Garcia JJ, Lopez-Pingarron L, Almeida-Souza P, Tres A, Escudero P, Garcia-Gil FA, Tan DX, Reiter RJ et al (2014) Protective effects of melatonin in reducing oxidative stress and in preserving the fluidity of biological membranes: a review. J Pineal Res 56(3):225–237. doi: 10.1111/jpi.12128 CrossRefPubMedGoogle Scholar
  26. 26.
    Zhang L, Zhang HQ, Liang XY, Zhang HF, Zhang T, Liu FE (2013) Melatonin ameliorates cognitive impairment induced by sleep deprivation in rats: role of oxidative stress, BDNF and CaMKII. Behav Brain Res 256:72–81. doi: 10.1016/j.bbr.2013.07.051 CrossRefPubMedGoogle Scholar
  27. 27.
    Chang HM, Wu UI, Lan CT (2009) Melatonin preserves longevity protein (sirtuin 1) expression in the hippocampus of total sleep-deprived rats. J Pineal Res 47(3):211–220. doi: 10.1111/j.1600-079X.2009.00704.x CrossRefPubMedGoogle Scholar
  28. 28.
    Olcese JM, Cao C, Mori T, Mamcarz MB, Maxwell A, Runfeldt MJ, Wang L, Zhang C et al (2009) Protection against cognitive deficits and markers of neurodegeneration by long-term oral administration of melatonin in a transgenic model of Alzheimer disease. J Pineal Res 47(1):82–96. doi: 10.1111/j.1600-079X.2009.00692.x CrossRefPubMedGoogle Scholar
  29. 29.
    Shaji AV, Kulkarni SK (1998) Evidence of GABAergic modulation in melatonin-induced short-term memory deficits and food consumption. Methods Find Exp Clin Pharmacol 20(4):311–319CrossRefPubMedGoogle Scholar
  30. 30.
    Alhaider IA, Aleisa AM, Tran TT, Alkadhi KA (2011) Sleep deprivation prevents stimulation-induced increases of levels of P-CREB and BDNF: protection by caffeine. Mol Cell Neurosci 46(4):742–751. doi: 10.1016/j.mcn.2011.02.006 CrossRefPubMedGoogle Scholar
  31. 31.
    Grahnstedt S, Ursin R (1985) Platform sleep deprivation affects deep slow wave sleep in addition to REM sleep. Behav Brain Res 18(3):233–239CrossRefPubMedGoogle Scholar
  32. 32.
    Alzoubi KH, Abdul-Razzak KK, Khabour OF, Al-Tuweiq GM, Alzubi MA, Alkadhi KA (2013) Caffeine prevents cognitive impairment induced by chronic psychosocial stress and/or high fat-high carbohydrate diet. Behav Brain Res 237:7–14. doi: 10.1016/j.bbr.2012.09.018 CrossRefPubMedGoogle Scholar
  33. 33.
    Diamond DM, Park CR, Heman KL, Rose GM (1999) Exposing rats to a predator impairs spatial working memory in the radial arm water maze. Hippocampus 9(5):542–552. doi: 10.1002/(SICI)1098-1063(1999)9:5<542::AID-HIPO8>3.0.CO;2-N CrossRefPubMedGoogle Scholar
  34. 34.
    Alzoubi KH, Khabour OF, Salah HA, Abu Rashid BE (2012) The combined effect of sleep deprivation and Western diet on spatial learning and memory: role of BDNF and oxidative stress. J Mol Neurosci. doi: 10.1007/s12031-012-9881-7 Google Scholar
  35. 35.
    Alzoubi KH, Gerges NZ, Aleisa AM, Alkadhi KA (2009) Levothyroxin restores hypothyroidism-induced impairment of hippocampus-dependent learning and memory: behavioral, electrophysiological, and molecular studies. Hippocampus 19(1):66–78. doi: 10.1002/hipo.20476 CrossRefPubMedGoogle Scholar
  36. 36.
    Khabour OF, Alzoubi KH, Alomari MA, Alzubi MA (2013) Changes in spatial memory and BDNF expression to simultaneous dietary restriction and forced exercise. Brain Res Bull 90:19–24. doi: 10.1016/j.brainresbull.2012.08.005 CrossRefPubMedGoogle Scholar
  37. 37.
    Alzoubi KH, Aleisa AM, Alkadhi KA (2006) Molecular studies on the protective effect of nicotine in adult-onset hypothyroidism-induced impairment of long-term potentiation. Hippocampus 16(10):861–874. doi: 10.1002/hipo.20217 CrossRefPubMedGoogle Scholar
  38. 38.
    Khabour OF, Alzoubi KH, Alomari MA, Alzubi MA (2010) Changes in spatial memory and BDNF expression to concurrent dietary restriction and voluntary exercise. Hippocampus 20(5):637–645. doi: 10.1002/hipo.20657 PubMedGoogle Scholar
  39. 39.
    Vollert C, Zagaar M, Hovatta I, Taneja M, Vu A, Dao A, Levine A, Alkadhi K et al (2011) Exercise prevents sleep deprivation-associated anxiety-like behavior in rats: potential role of oxidative stress mechanisms. Behav Brain Res 224(2):233–240. doi: 10.1016/j.bbr.2011.05.010 CrossRefPubMedGoogle Scholar
  40. 40.
    McCord MC, Aizenman E (2014) The role of intracellular zinc release in aging, oxidative stress, and Alzheimer’s disease. Front Aging Neurosci 6:77. doi: 10.3389/fnagi.2014.00077 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Forero DA, Casadesus G, Perry G, Arboleda H (2006) Synaptic dysfunction and oxidative stress in Alzheimer’s disease: emerging mechanisms. J Cell Mol Med 10(3):796–805CrossRefPubMedGoogle Scholar
  42. 42.
    Gupta YK, Gupta M, Kohli K (2003) Neuroprotective role of melatonin in oxidative stress vulnerable brain. Indian J Physiol Pharmacol 47(4):373–386PubMedGoogle Scholar
  43. 43.
    Patel RP TC, Darley-Usmar VM (1999) The biochemistry of nitric oxide and peroxynitrite: implication for mitochondrial function. In: Packer L, Cadenas E (eds) Understanding the process of aging: the roles of mitochondria, free radicals, and antioxidants. Marcel Dekker, New York, pp 39–56Google Scholar
  44. 44.
    Zelko IN, Mariani TJ, Folz RJ (2002) Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med 33(3):337–349CrossRefPubMedGoogle Scholar
  45. 45.
    Chelikani P, Fita I, Loewen PC (2004) Diversity of structures and properties among catalases. Cell Mol Life Sci 61(2):192–208. doi: 10.1007/s00018-003-3206-5 CrossRefPubMedGoogle Scholar
  46. 46.
    Meister AAM (1983) Glutathione. Annu Rev Biochem 52:711–760CrossRefPubMedGoogle Scholar
  47. 47.
    Benzi G, Marzatico F, Pastoris O, Villa RF (1990) Influence of oxidative stress on the age-linked alterations of the cerebral glutathione system. J Neurosci Res 26(1):120–128. doi: 10.1002/jnr.490260116 CrossRefPubMedGoogle Scholar
  48. 48.
    Fukui K, Omoi NO, Hayasaka T, Shinnkai T, Suzuki S, Abe K, Urano S (2002) Cognitive impairment of rats caused by oxidative stress and aging, and its prevention by vitamin E. Ann N Y Acad Sci 959:275–284CrossRefPubMedGoogle Scholar
  49. 49.
    Jhoo JH, Kim HC, Nabeshima T, Yamada K, Shin EJ, Jhoo WK, Kim W, Kang KS et al (2004) Beta-amyloid (1–42)-induced learning and memory deficits in mice: involvement of oxidative burdens in the hippocampus and cerebral cortex. Behav Brain Res 155(2):185–196. doi: 10.1016/j.bbr.2004.04.012 CrossRefPubMedGoogle Scholar
  50. 50.
    Markesbery WR (1997) Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med 23(1):134–147CrossRefPubMedGoogle Scholar
  51. 51.
    Markesbery WR, Lovell MA (1998) Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer’s disease. Neurobiol Aging 19(1):33–36CrossRefPubMedGoogle Scholar
  52. 52.
    Butterfield DA, Drake J, Pocernich C, Castegna A (2001) Evidence of oxidative damage in Alzheimer’s disease brain: central role for amyloid beta-peptide. Trends Mol Med 7(12):548–554CrossRefPubMedGoogle Scholar
  53. 53.
    Lauderback CM, Hackett JM, Huang FF, Keller JN, Szweda LI, Markesbery WR, Butterfield DA (2001) The glial glutamate transporter, GLT-1, is oxidatively modified by 4-hydroxy-2-nonenal in the Alzheimer’s disease brain: the role of Abeta1-42. J Neurochem 78(2):413–416CrossRefPubMedGoogle Scholar
  54. 54.
    Lovell MA, Markesbery WR (2001) Ratio of 8-hydroxyguanine in intact DNA to free 8-hydroxyguanine is increased in Alzheimer disease ventricular cerebrospinal fluid. Arch Neurol 58(3):392–396CrossRefPubMedGoogle Scholar
  55. 55.
    Aiguo W, Zhe Y, Gomez-Pinilla F (2010) Vitamin E protects against oxidative damage and learning disability after mild traumatic brain injury in rats. Neurorehabil Neural Repair 24(3):290–298. doi: 10.1177/1545968309348318 CrossRefGoogle Scholar
  56. 56.
    Nicolle MM, Gonzalez J, Sugaya K, Baskerville KA, Bryan D, Lund K, Gallagher M, McKinney M (2001) Signatures of hippocampal oxidative stress in aged spatial learning-impaired rodents. Neuroscience 107(3):415–431CrossRefPubMedGoogle Scholar
  57. 57.
    Yang X, Yang Y, Fu Z, Li Y, Feng J, Luo J, Zhang Q, Wang Q et al (2011) Melatonin ameliorates Alzheimer-like pathological changes and spatial memory retention impairment induced by calyculin A. J Psychopharmacol 25(8):1118–1125. doi: 10.1177/0269881110367723 CrossRefPubMedGoogle Scholar
  58. 58.
    He P, Ouyang X, Zhou S, Yin W, Tang C, Laudon M, Tian S (2013) A novel melatonin agonist Neu-P11 facilitates memory performance and improves cognitive impairment in a rat model of Alzheimer’ disease. Horm Behav 64(1):1–7. doi: 10.1016/j.yhbeh.2013.04.009 CrossRefPubMedGoogle Scholar
  59. 59.
    Ali T, Badshah H, Kim TH, Kim MO (2015) Melatonin attenuates D-galactose-induced memory impairment, neuroinflammation and neurodegeneration via RAGE/NF-K B/JNK signaling pathway in aging mouse model. J Pineal Res 58(1):71–85. doi: 10.1111/jpi.12194 CrossRefPubMedGoogle Scholar
  60. 60.
    Saxena G, Bharti S, Kamat PK, Sharma S, Nath C (2010) Melatonin alleviates memory deficits and neuronal degeneration induced by intracerebroventricular administration of streptozotocin in rats. Pharmacol Biochem Behav 94(3):397–403. doi: 10.1016/j.pbb.2009.09.022 CrossRefPubMedGoogle Scholar
  61. 61.
    Ozdemir D, Tugyan K, Uysal N, Sonmez U, Sonmez A, Acikgoz O, Ozdemir N, Duman M et al (2005) Protective effect of melatonin against head trauma-induced hippocampal damage and spatial memory deficits in immature rats. Neurosci Lett 385(3):234–239. doi: 10.1016/j.neulet.2005.05.055 CrossRefPubMedGoogle Scholar
  62. 62.
    Baydas G, Ozveren F, Akdemir I, Tuzcu M, Yasar A (2005) Learning and memory deficits in rats induced by chronic thinner exposure are reversed by melatonin. J Pineal Res 39(1):50–56. doi: 10.1111/j.1600-079X.2005.00212.x CrossRefPubMedGoogle Scholar
  63. 63.
    Mehta KD, Mehta AK, Halder S, Khanna N, Tripathi AK, Sharma KK (2014) Protective effect of melatonin on propoxur-induced impairment of memory and oxidative stress in rats. Environ Toxicol 29(6):705–713. doi: 10.1002/tox.21798 CrossRefPubMedGoogle Scholar
  64. 64.
    Tongjaroenbuangam W, Ruksee N, Mahanam T, Govitrapong P (2013) Melatonin attenuates dexamethasone-induced spatial memory impairment and dexamethasone-induced reduction of synaptic protein expressions in the mouse brain. Neurochem Int 63(5):482–491. doi: 10.1016/j.neuint.2013.08.011 CrossRefPubMedGoogle Scholar
  65. 65.
    Reiter RJ, Tan DX, Osuna C, Gitto E (2000) Actions of melatonin in the reduction of oxidative stress. A review. J Biomed Sci 7(6):444–458CrossRefPubMedGoogle Scholar
  66. 66.
    Reiter RJ, Calvo JR, Karbownik M, Qi W, Tan DX (2000) Melatonin and its relation to the immune system and inflammation. Ann N Y Acad Sci 917:376–386CrossRefPubMedGoogle Scholar
  67. 67.
    Hotchkiss AK, Nelson RJ (2002) Melatonin and immune function: hype or hypothesis? Crit Rev Immunol 22(5–6):351–371PubMedGoogle Scholar
  68. 68.
    Reiter RJ, Tan DX, Manchester LC, El-Sawi MR (2002) Melatonin reduces oxidant damage and promotes mitochondrial respiration: implications for aging. Ann N Y Acad Sci 959:238–250CrossRefPubMedGoogle Scholar
  69. 69.
    Poeggeler B, Saarela S, Reiter RJ, Tan DX, Chen LD, Manchester LC, Barlow-Walden LR (1994) Melatonin—a highly potent endogenous radical scavenger and electron donor: new aspects of the oxidation chemistry of this indole accessed in vitro. Ann N Y Acad Sci 738:419–420CrossRefPubMedGoogle Scholar
  70. 70.
    Rodriguez AB, Nogales G, Marchena JM, Ortega E, Barriga C (1999) Suppression of both basal and antigen-induced lipid peroxidation in ring dove heterophils by melatonin. Biochem Pharmacol 58(8):1301–1306CrossRefPubMedGoogle Scholar
  71. 71.
    Terron MP, Marchena JM, Shadi F, Harvey S, Lea RW, Rodriguez AB (2001) Melatonin: an antioxidant at physiological concentrations. J Pineal Res 31(1):95–96CrossRefPubMedGoogle Scholar
  72. 72.
    Tan DX, Manchester LC, Terron MP, Flores LJ, Reiter RJ (2007) One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species? J Pineal Res 42(1):28–42. doi: 10.1111/j.1600-079X.2006.00407.x CrossRefPubMedGoogle Scholar
  73. 73.
    Winiarska K, Fraczyk T, Malinska D, Drozak J, Bryla J (2006) Melatonin attenuates diabetes-induced oxidative stress in rabbits. J Pineal Res 40(2):168–176. doi: 10.1111/j.1600-079X.2005.00295.x CrossRefPubMedGoogle Scholar
  74. 74.
    Leon J, Acuna-Castroviejo D, Escames G, Tan DX, Reiter RJ (2005) Melatonin mitigates mitochondrial malfunction. J Pineal Res 38(1):1–9. doi: 10.1111/j.1600-079X.2004.00181.x CrossRefPubMedGoogle Scholar
  75. 75.
    Ramanathan L, Hu S, Frautschy SA, Siegel JM (2010) Short-term total sleep deprivation in the rat increases antioxidant responses in multiple brain regions without impairing spontaneous alternation behavior. Behav Brain Res 207(2):305–309. doi: 10.1016/j.bbr.2009.10.014 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Karem H. Alzoubi
    • 1
    Email author
  • Fadia A. Mayyas
    • 1
  • Omar F. Khabour
    • 2
    • 3
  • Fatima M. Bani Salama
    • 1
  • Farah H. Alhashimi
    • 1
  • Nizar M. Mhaidat
    • 1
  1. 1.Department of Clinical Pharmacy, Faculty of PharmacyJordan University of Science and TechnologyIrbidJordan
  2. 2.Department of Medical Laboratory Sciences, Faculty of Applied Medical SciencesJordan University of Science and TechnologyIrbidJordan
  3. 3.Department of Biology, Faculty of ScienceTaibah UniversityMedinaSaudi Arabia

Personalised recommendations