jnbs The Journal of Neurobehavioral Sciences 2149-1909 2148-4325 Uskudar University 10.32739/jnbs.13.1.283 Central Nervous System Merkezi Sinir Sistemi Sleep Recovery Improves Cognitive Function and Reduces Oxidative Stress and Beta-Amyloid Expression in the Hippocampus of Total Sleep-Deprived Adult Male Wistar Rats Sleep Recovery Improves Cognitive Function and Reduces Oxidative Stress and Beta-Amyloid Expression in the Hippocampus of Total Sleep-Deprived Adult Male Wistar Rats https://orcid.org/0000-0002-9454-2526 Ekpo Ubong Ahmadu Bello University, Zaria, Kaduna, Nigeria https://orcid.org/0000-0003-2096-7238 Umana Uduak Ahmadu Bello University, Zaria https://orcid.org/0000-0001-5883-3425 Sadeeq Abubakar Ahmadu Bello University, Zaria https://orcid.org/0000-0002-2530-8322 Sambo Sohnap Ahmadu Bello University, Zaria 03 31 2026 13 1 8 17 11 03 2025 03 23 2026 Copyright © 2014, The Journal of Neurobehavioral Sciences 2014 The Journal of Neurobehavioral Sciences

Background: Lack of sleep has been linked in studies to increased beta-amyloid levels, oxidative stress, and memory impairments. Furthermore, sleep is known to help clear toxins that accumulate in the brain. Aim: This study investigated the restorative potentials of recovery sleep on total sleep deprivation-induced memory impairment, oxidative stress and changes in beta amyloid plaques in the hippocampus of adult male Wistar rats. Materials and Methods: Twenty-four male Wistar rats weighing between 150 and 200 g were divided into four groups. Group I remained in their home cages, while Groups II, III, and IV underwent sleep deprivation for 5 days. Groups III and IV then had recovery periods of 7 and 21 days, respectively. Spatial learning and memory was measured using the Morris Water Maze test. The rats were euthanized with ketamine, oxidative stress was analyzed using hippocampal tissue homogenate and beta-amyloid plaques in the CA1 and CA3 regions using Congo red stain. Results: Comparing the sleep-deprived group to the sleep-recovered group, the discrimination ratio increased significantly (p < 0.0001). Sleep recovery also decreased levels of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and malonaldehyde (MDA) and corticosterone (p < 0.01). Additionally, extracellular amyloid-beta expression in the CA1 and CA3 regions of the sleep recovery groups was significantly reduced (p < 0.0001 and p < 0.01). Conclusion: Recovery sleep was found to improve memory and decrease beta amyloid expression and oxidative stress in the CA1 and CA3 areas of the hippocampus.

Background: Lack of sleep has been linked in studies to increased beta-amyloid levels, oxidative stress, and memory impairments. Furthermore, sleep is known to help clear toxins that accumulate in the brain. Aim: This study investigated the restorative potentials of recovery sleep on total sleep deprivation-induced memory impairment, oxidative stress and changes in beta amyloid plaques in the hippocampus of adult male Wistar rats. Materials and Methods: Twenty-four male Wistar rats weighing between 150 and 200 g were divided into four groups. Group I remained in their home cages, while Groups II, III, and IV underwent sleep deprivation for 5 days. Groups III and IV then had recovery periods of 7 and 21 days, respectively. Spatial learning and memory was measured using the Morris Water Maze test. The rats were euthanized with ketamine, oxidative stress was analyzed using hippocampal tissue homogenate and beta-amyloid plaques in the CA1 and CA3 regions using Congo red stain. Results: Comparing the sleep-deprived group to the sleep-recovered group, the discrimination ratio increased significantly (p < 0.0001). Sleep recovery also decreased levels of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and malonaldehyde (MDA) and corticosterone (p < 0.01). Additionally, extracellular amyloid-beta expression in the CA1 and CA3 regions of the sleep recovery groups was significantly reduced (p < 0.0001 and p < 0.01). Conclusion: Recovery sleep was found to improve memory and decrease beta amyloid expression and oxidative stress in the CA1 and CA3 areas of the hippocampus.

 Sleep deprivation sleep recovery memory deficit oxidative stress beta amyloid Sleep deprivation sleep recovery memory deficit oxidative stress beta amyloid Ahmadu Bello University, Zaria ABUCAUC/2024/034 1. Medic G, Wille M, Hemels ME. Short- and long-term health consequences of sleep disruption. Nat Sci Sleep. 2017;9:151-161. doi: 10.2147/NSS.S134864 [1]. 2. Kordestani-Moghadam P, Nasehi M, Vaseghi S, Khodagholi F, Zarrindast MR. The role of sleep disturbances in depressive-like behavior with emphasis on α-ketoglutarate dehydrogenase activity in rats. Physiol Behav. 2020;224:113023. doi: 10.1016/j.physbeh.2020.113023 [2]. 3. Mahdavi MS, Nasehi M, Vaseghi S, Mousavi Z, Zarrindast MR. The effect of alpha lipoic acid on passive avoidance and social interaction memory, pain perception, and locomotor activity in REM sleep-deprived rats. Pharmacol Rep. 2021;73(1):102-110. doi: 10.1007/s43440-020-00161-8 [3]. 4. Eydipour Z, Nasehi M, Vaseghi S, Jamaldini SH, Zarrindast MR. The role of 5-HT4 serotonin receptors in the CA1 hippocampal region on memory acquisition impairment induced by total (TSD) and REM sleep deprivation (RSD). Physiol Behav. 2020;215:112788. doi: 10.1016/j.physbeh.2019.112788 [4]. 5. Javad-Moosavi BZ, Nasehi M, Vaseghi S, Jamaldini SH, Zarrindast MR. Activation and inactivation of nicotinic receptors in the dorsal hippocampal region restored negative effects of total (TSD) and REM sleep deprivation (RSD) on memory acquisition, locomotor activity and pain perception. Neuroscience. 2020;433:200-211. doi: 10.1016/j.neuroscience.2020.03.006 [5]. 6. Zhang J, Zhang L, Chang Y, et al. The endocannabinoid system contributes to memory deficits induced by rapid-eye-movement sleep deprivation in adolescent mice. Neuroscience. 2020;433:174-183. doi: 10.1016/j.neuroscience.2020.03.016 [6]. 7. Kreutzmann JC, Havekes R, Abel T, Meerlo P. Sleep deprivation and hippocampal vulnerability: changes in neuronal plasticity, neurogenesis and cognitive function. Neuroscience. 2015;309:173-190. doi: 10.1016/j.neuroscience.2015.04.053 [7]. 8. Klinzing JG, Niethard N, Born J. Mechanisms of systems memory consolidation during sleep. Nat Neurosci. 2019;22(10):1598-1610. doi: 10.1038/s41593-019-0467-3 [8]. 9. Maggio M, Colizzi E, Fisichella A, et al. Stress hormones, sleep deprivation and cognition in older adults. Maturitas. 2013;76(1):22-44. doi: 10.1016/j.maturitas.2013.06.006 [9]. 10. Aliahmat NS, Noor MRM, Yusof WJW, Makpol S, Ngah WZW, Yusof YAM. Antioxidant enzyme activity and malondialdehyde levels can be modulated by Piper betle, tocotrienol rich fraction and Chlorella vulgaris in aging C57BL/6 mice. Clinics (Sao Paulo). 2012;67(12):1447-1454. doi: 10.6061/clinics/2012(12)16 [10]. 11. Davinelli S, Medoro A, Savino R, Scapagnini G. Sleep and oxidative stress: current perspectives on the role of NRF2. Cell Mol Neurobiol. 2024;44(1):52. doi: 10.1007/s10571-023-01375-0 12. Chen S, Xie Y, Li Y, et al. Sleep deprivation and recovery sleep affect healthy male resident’s pain sensitivity and oxidative stress markers: The medial prefrontal cortex may play a role in sleep deprivation model. Front Mol Neurosci. 2022;15:937468. doi: 10.3389/fnmol.2022.937468 13. Volicer L. Physiological and pathological functions of beta-amyloid in the brain and Alzheimer's disease: a review. J Physiol Invest. 2020;63(3):95-100. doi: 10.1007/s40279-019-01234-z 14. Kang JE, Lim MM, Bateman RJ, et al. Amyloid-β dynamics are regulated by orexin and the sleep-wake cycle. Science. 2009;326(5955):1005-1007. doi: 10.1126/science.1183913 15. Tabuchi M, Lone SR, Liu S, et al. Sleep interacts with aβ to modulate intrinsic neuronal excitability. Curr Biol. 2015;25(6):702-712. doi: 10.1016/j.cub.2015.01.058 16. Spira AP, Gamaldo AA, An Y, et al. Self-reported sleep and β-amyloid deposition in community-dwelling older adults. JAMA Neurol. 2013;70(12):1537-1543. doi: 10.1001/jamaneurol.2013.4250 17. Sprecher KE, Bendlin BB, Racine AM, et al. Amyloid burden is associated with self-reported sleep in nondemented late middle-aged adults. Neurobiol Aging. 2015;36(9):2568-2576. doi: 10.1016/j.neurobiolaging.2015.05.010 18. Ju YES, Lucey BP, Holtzman DM. Sleep and Alzheimer disease pathology—a bidirectional relationship. Nat Rev Neurol. 2014;10(2):115-119. doi: 10.1038/nrneurol.2013.269 19. Donohue MC, Sperling RA, Petersen R, et al. Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons. JAMA. 2017;317(22):2305-2316. doi: 10.1001/jama.2017.6665 20. Sauvet F, Florence G, Van Beers P, et al. Total sleep deprivation alters endothelial function in rats: A nonsympathetic mechanism. Sleep. 2014;37(3):465-473. doi: 10.5665/sleep.3472 21. Arjadi F, Wisesa S, Indriani V. Total sleep deprivation reduces quality of spermatozoa in male albino rat (Rattus norvegicus). Berkala Kedokteran. 2019;19(1):69-78. doi: 10.20473/bk.v19i1.14542 22. Machado RB, Hipólide DC, Benedito-Silva AA, Tufik S. Sleep deprivation induced by the modified multiple platform technique: Quantification of sleep loss and recovery. Brain Res. 2004;1004(1-2):45-51. doi: 10.1016/j.brainres.2004.01.014 23. Lueptow LM. Novel object recognition test for the investigation of learning and memory in mice. J Vis Exp. 2017;(126):e55718. doi: 10.3791/55718 24. Chen Y, Chen Z, Chen W. Altered hippocampal neurogenesis in chronic neuropathic pain. Neural Plast. 2021;2021:6676074. doi: 10.1155/2021/6676074 25. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351-358. doi: 10.1016/0003-2697(79)90738-3 26. Atawodi SE, Atawodi JC, Idakwo GA, et al. Evaluation of the polyphenol content and antioxidant properties of methanol extracts of the leaves, stem, and root barks of Moringa oleifera Lam. J Med Food. 2011;14(9):1003-1013. doi: 10.1089/jmf.2010.0199 27. Abebi AO. Catalase activity in tissues of some Nigerian livestock. Comp Biochem Physiol B. 1974;49(3):579-585. doi: 10.1016/0305-0491(74)90262-6 28. Fridovich I. Superoxide dismutases. Adv Enzymol Relat Areas Mol Biol. 1989;62:345-382. 29. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959;82(1):70-77. doi: 10.1016/0003-9861(59)90090-6 30. Schmidt A, Wacker M, Wehling M, Schwabe K. Congo red and protein aggregation in neurodegenerative diseases. Brain Res Rev. 2010;63(1-2):75-92. doi: 10.1016/j.brainresrev.2009.10.001 31. Prince TM, Abel T. The impact of sleep loss on hippocampal function. Learn Mem. 2013;20(10):558-569. doi: 10.1101/lm.032744.113 32. Delorme J, Wang L, Kuhn FR, et al. Sleep loss drives acetylcholine-and somatostatin interneuron–mediated gating of hippocampal activity to inhibit memory consolidation. Proc Natl Acad Sci U S A. 2021;118(32):e2019318118. doi: 10.1073/pnas.2019318118 33. Cohen SJ, Stackman RW Jr. Assessing rodent hippocampal involvement in the novel object recognition task. A review. Behav Brain Res. 2015;285:105-117. doi: 10.1016/j.bbr.2015.02.003 34. Ennaceur A. One-trial object recognition in rats and mice: methodological and theoretical issues. Behav Brain Res. 2010;215(2):244-254. doi: 10.1016/j.bbr.2010.07.020 35. Campbell I, Guinan MJ, Horowitz JM. Sleep deprivation impairs long-term potentiation in rat hippocampal slices. J Neurophysiol. 2002;88(2):1073-1076. doi: 10.1152/jn.2002.88.2.1073 36. Chen P, Ban W, Wang W, You Y, Yang Z. The devastating effects of sleep deprivation on memory: lessons from rodent models. Clocks Sleep. 2023;5(2):276-294. doi: 10.3390/clockssleep5020020 37. Palchykova S, Winsky-Sommerer R, Meerlo P, Dürr R, Tobler I. Sleep deprivation impairs object recognition in mice. Neurobiol Learn Mem. 2006;85(3):263-271. doi: 10.1016/j.nlm.2005.11.012 38. Cordeira J, Kolluru SS, Rosenblatt H, Kry J, Strecker RE, McCarley RW. Learning and memory are impaired in the object recognition task during metestrus/diestrus and after sleep deprivation. Behav Brain Res. 2018;339:124-129. doi: 10.1016/j.bbr.2017.11.011 39. Shahveisi K, Farnia V, Khazaie H, Ghazvini H, Nozari M, Khodamoradi M. Novel object recognition memory in REM sleep-deprived rats: Role of the cannabinoid CB1 receptor. Behav Brain Res. 2020;381:112311. doi: 10.1016/j.bbr.2020.112311 40. Fluke S, Satterfield B, Davis C. Sleep Deprivation Impairs Short-Term Object Recall On A Serial Novel Object Recognition Task In Rats. Sleep. 2024;47(Supplement_1):A324-A325. doi: 10.1093/sleep/zsae108.817 41. Sara SJ. Reactivation, retrieval, replay and reconsolidation in and out of sleep: connecting the dots. Front Behav Neurosci. 2010;4:185. doi: 10.3389/fnbeh.2010.00185 42. Ma Y, Liang L, Zheng F, Shi L, Zhong B, Xie W. Association between sleep duration and cognitive decline. JAMA Netw Open. 2020;3(9):e2013573. doi: 10.1001/jamanetworkopen.2020.13573 43. Stickgold R, Walker MP. Sleep-dependent memory consolidation and reconsolidation. Sleep Med. 2007;8(4):331-343. doi: 10.1016/j.sleep.2006.12.002 44. Fan Y, Li J, Qiao S. Sleep deprivation-induced memory impairment: exploring potential interventions. Front Psychiatry. 2024;15:1470976. doi: 10.3389/fpsyt.2024.1470976 45. Binder S, Baier PC, Mölle M, Inostroza M, Born J, Marshall L. Sleep enhances memory consolidation in the hippocampus-dependent object-place recognition task in rats. Neurobiol Learn Mem. 2012;97(2):213-219. doi: 10.1016/j.nlm.2011.12.009 46. Adwas AA, Elsayed A, Azab AE, Quwaydir FA. Oxidative stress and antioxidant mechanisms in human body. J Appl Biotechnol Bioeng. 2019;6(1):43-47. doi: 10.15406/jabb.2019.06.00171 47. Pizzino G, Irrera N, Cucinotta M, et al. Oxidative stress: harms and benefits for human health. Oxid Med Cell Longev. 2017;2017:8416763. doi: 10.1155/2017/8416763 48. Singh P, Barman B, Thakur MK. Oxidative stress-mediated memory impairment during aging and its therapeutic intervention by natural bioactive compounds. Front Aging Neurosci. 2022;14:944697. doi: 10.3389/fnagi.2022.944697 49. Salim S. Oxidative stress and the central nervous system. J Pharmacol Exp Ther. 2017;360(1):201-205. doi: 10.1124/jpet.116.237503 50. Gao YZ, Liu K, Wu XM, et al. Oxidative stress-mediated loss of hippocampal parvalbumin interneurons contributes to memory precision decline after acute sleep deprivation. Mol Neurobiol. 2025;62(5):5377-5394. doi: 10.1007/s12035-025-00133-6 51. Feng L, Wu HW, Song GQ, et al. Chronical sleep interruption-induced cognitive decline assessed by a metabolomics method. Behav Brain Res. 2016;302:60-68. doi: 10.1016/j.bbr.2016.01.003 52. Gilley RR. The role of sleep in cognitive function: the value of a good night’s rest. Clin EEG Neurosci. 2023;54(1):12-20. doi: 10.1177/15500594221134471 53. Kowalczyk P, Sulejczak D, Kleczkowska P, et al. Mitochondrial oxidative stress—a causative factor and therapeutic target in many diseases. Int J Mol Sci. 2021;22(24):13384. doi: 10.3390/ijms222413384 54. Hartmann C, Kempf A. Mitochondrial control of sleep. Curr Opin Neurobiol. 2023;81:102733. doi: 10.1016/j.conb.2023.102733 55. Andreazza AC, Andersen ML, Alvarenga TA, et al. Impairment of the mitochondrial electron transport chain due to sleep deprivation in mice. J Psychiatr Res. 2010;44(12):775-780. doi: 10.1016/j.jpsychires.2009.12.008 56. Atrooz F, Salim S. Sleep deprivation, oxidative stress, and inflammation. Adv Protein Chem Struct Biol. 2020;119:309-336. doi: 10.1016/bs.apcsb.2019.07.002 57. Coluk Y, Yildirim G, Yildirmak S, Peker EGG. Altered brain-derived neurotrophic factor levels and oxidative stress in REM sleep deprivation: a rat model study. BMC Neurol. 2025;25(1):1-9. doi: 10.1186/s12883-024-03579-8 58. Bafana A, Dutt S, Kumar A, Kumar S, Ahuja PS. The basic and applied aspects of superoxide dismutase. J Mol Catal B Enzym. 2011;68(2):129-138. doi: 10.1016/j.molcatb.2010.10.004 59. Zheng M, Liu Y, Zhang G, Yang Z, Xu W, Chen Q. The applications and mechanisms of superoxide dismutase in medicine, food, and cosmetics. Antioxidants (Basel). 2023;12(9):1675. doi: 10.3390/antiox12091675 60. Anwar S, Alrumaihi F, Sarwar T, et al. Exploring therapeutic potential of catalase: Strategies in disease prevention and management. Biomolecules. 2024;14(6):697. doi: 10.3390/biom14060697 61. Mathangi DC, Shyamala R, Subhashini AS. Effect of REM sleep deprivation on the antioxidant status in the brain of Wistar rats. Ann Neurosci. 2012;19(4):161. 62. Ramamoorthy S, Cidlowski JA. Corticosteroids-mechanisms of action in health and disease. Rheum Dis Clin North Am. 2016;42(1):15. doi: 10.1016/j.rdc.2015.08.004 63. Yang J, Liu L, Sheikhahmadi A, et al. Effects of corticosterone and dietary energy on immune function of broiler chickens. PLoS One. 2015;10(3):e0119750. doi: 10.1371/journal.pone.0119750 64. Elenkov IJ, Webster EL, Torpy DJ, Chrousos GP. Stress, Corticotropin‐Releasing Hormone, Glucocorticoids, and the Immune/Inflammatory Response: Acute and Chronic Effects a. Ann N Y Acad Sci. 1999;876(1):1-13. doi: 10.1111/j.1749-6632.1999.tb07268.x 65. Nollet M, Wisden W, Franks NP. Sleep deprivation and stress: a reciprocal relationship. Interface Focus. 2020;10(3):20190092. doi: 10.1098/rsfs.2019.0092 66. Thompson KI, Chau M, Lorenzetti MS, Hill LD, Fins AI, Tartar JL. Acute sleep deprivation disrupts emotion, cognition, inflammation, and cortisol in young healthy adults. Front Behav Neurosci. 2022;16:945661. doi: 10.3389/fnbeh.2022.945661 67. Machado RB, Tufik S, Suchecki D. Role of corticosterone on sleep homeostasis induced by REM sleep deprivation in rats. PLoS One. 2013;8(5):e63520. doi: 10.1371/journal.pone.0063520 68. Gao Y, Akers B, Roberts MB, El-Mallakh RS. Corticosterone response in sleep deprivation and sleep fragmentation. J Sleep Disord Manag. 2017;3:18. 69. Tartar JL, Ward CP, Cordeira JW, Legare SL, Blanchette AJ, McCarley RW, Strecker RE. Experimental sleep fragmentation and sleep deprivation in rats increases exploration in an open field test of anxiety while increasing plasma corticosterone levels. Behav Brain Res. 2009;197(2):450-453. doi: 10.1016/j.bbr.2008.07.037 70. Chen S, Xie Y, Liang Z, et al. A narrative review of the reciprocal relationship between sleep deprivation and chronic pain: the role of oxidative stress. J Pain Res. 2024;17:1785-1792. doi: 10.2147/JPR.S449439 71. Nicolaides NC, Vgontzas AN, Kritikou I, Chrousos G. HPA axis and sleep. Endotext [Internet]. 2020. 72. Balbo M, Leproult R, Van Cauter E. Impact of sleep and its disturbances on hypothalamo‐pituitary‐adrenal axis activity. Int J Endocrinol. 2010;2010(1):759234. doi: 10.1155/2010/759234 73. Vgontzas AN, Mastorakos G, Bixler EO, Kales A, Gold PW, Chrousos GP. Sleep deprivation effects on the activity of the hypothalamic–pituitary–adrenal and growth axes: potential clinical implications. Clin Endocrinol. 1999;51(2):205-215. doi: 10.1046/j.1365-2265.1999.00781.x 74. Voderholzer U, Hohagen F, Klein T, et al. Impact of sleep deprivation and subsequent recovery sleep on cortisol in unmedicated depressed patients. Am J Psychiatry. 2004;161(8):1404-1410. doi: 10.1176/appi.ajp.161.8.1404 75. Meerlo P, Koehl M, Van der Borght K, Turek FW. Sleep restriction alters the hypothalamic‐pituitary‐adrenal response to stress. J Neuroendocrinol. 2002;14(5):397-402. doi: 10.1046/j.1365-2826.2002.00796.x 76. Westmark CJ. What’s hAPPening at synapses? The role of amyloid β-protein precursor and β-amyloid in neurological disorders. Mol Psychiatry. 2013;18(4):425-434. doi: 10.1038/mp.2012.24 77. Penke B, Bogár F, Fülöp L. β-Amyloid and the pathomechanisms of Alzheimer’s disease: a comprehensive view. Molecules. 2017;22(10):1692. doi: 10.3390/molecules22101692 78. Cordone S, Annarumma L, Rossini PM, De Gennaro L. Sleep and β-amyloid deposition in Alzheimer disease: insights on mechanisms and possible innovative treatments. Front Pharmacol. 2019;10:695. doi: 10.3389/fphar.2019.00695 79. Voumvourakis KI, Sideri E, Papadimitropoulos GN, et al. The dynamic relationship between the glymphatic system, aging, memory, and sleep. Biomedicines. 2023;11(8):2092. doi: 10.3390/biomedicines11082092 80. Reiter RJ, Sharma R, Cucielo MS, et al. Brain washing and neural health: role of age, sleep, and the cerebrospinal fluid melatonin rhythm. Cell Mol Life Sci. 2023;80(4):88. doi: 10.1007/s00018-023-04751-y 81. Lee YF, Gerashchenko D, Timofeev I, Bacskai BJ, Kastanenka KV. Slow wave sleep is a promising intervention target for Alzheimer’s disease. Front Neurosci. 2020;14:705. doi: 10.3389/fnins.2020.00705 82. Han Z, Yang X, Huang S. Sleep deprivation: A risk factor for the pathogenesis and progression of Alzheimer's disease. Heliyon. 2024;10(7). doi: 10.1016/j.heliyon.2024.e29693 83. Shokri-Kojori E, Wang GJ, Wiers CE, et al. β-Amyloid accumulation in the human brain after one night of sleep deprivation. Proc Natl Acad Sci U S A. 2018;115(17):4483-4488. doi: 10.1073/pnas.1721694115 84. Brown BM, Rainey-Smith SR, Villemagne VL, et al. The relationship between sleep quality and brain amyloid burden. Sleep. 2016;39(5):1063-1068. doi: 10.5665/sleep.3666 85. Xie L, Kang H, Xu Q, et al. Sleep drives metabolite clearance from the adult brain. Science. 2013;342(6156):373-377. doi: 10.1126/science.1241224 86. Ooms S, Overeem S, Besse K, Rikkert MO, Verbeek M, Claassen JA. Effect of 1 night of total sleep deprivation on cerebrospinal fluid β-amyloid 42 in healthy middle-aged men: a randomized clinical trial. JAMA Neurol. 2014;71(8):971-977. doi: 10.1001/jamaneurol.2014.794 87. Ju YES, Ooms SJ, Sutphen C, et al. Slow wave sleep disruption increases cerebrospinal fluid amyloid-β levels. Brain. 2017;140(8):2104-2111. doi: 10.1093/brain/awx148 88. Ema E, Mohammad A, Ekpo UU, Oderinde GP, Usman A. Evaluation of the effects of cannabidiol and sleep recovery on oxidative stress biomarkers and testicular histoarchitecture in chronic sleep-deprived male Wistar rats. Dutse J Pure Appl Sci. 2025;11(2d):328-338.