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Combined Exposure to Chronic Sleep Deprivation and Caffeine Potentiates Behavioural Deficits by Altering Neurochemical Profile and Synaptophysin Expression in Long-Evans Rats

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Abstract

Using the Unpredictable Chronic Sleep Deprivation (UCSD) paradigm we developed, the combined effects of chronic sleep deprivation and high caffeine intake on prefrontal cortical synaptophysin expression, neurochemical profiles, and behavioural outcomes in Long-Evans rats were evaluated. The combination of chronic sleep deprivation and high-dose caffeine treatment produced varying degrees of behavioural impairments, depletion of antioxidants, serotonin, and an upregulation of acetylcholinesterase (AChE) activity in the prefrontal cortex. An immunohistochemical assessment revealed a reduction in synaptophysin protein expression in the prefrontal cortex following exposure to high-dose caffeine and chronic sleep deprivation. Overall, our findings support the advocacy for adequate sleep for optimal mental performance as a high intake of caffeine to attenuate the effects of sleep deprivation that may alter the neurochemical profile and synaptic plasticity in the prefrontal cortex, significantly increasing the risk of neuropsychiatric/degenerative disorders.

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References

  • Acevedo J, Santana-Almansa A, Matos-Vergara N, Marrero-Cordero LR, Cabezas-Bou E, Díaz-Ríos M (2016) Caffeine stimulates locomotor activity in the mammalian spinal cord via adenosine A1 receptor-dopamine D1 receptor interaction and PKA-dependent mechanisms. Neuropharmacology Pergamon 101:490–505

    Article  CAS  Google Scholar 

  • Adewole O (2017) Pattern of sleep disorders among patients in a Nigerian family practice population. Ann Med Health Sci Res. Annals of Medical and Health Sciences Research

  • Ademola O, Edem E, Olufunke D, Oladunni K (2016) Cognitive-enhancing and neurotherapeutic prospects of viscum album in experimental model of Alzheimer's disease. Off J Soc Cell Pathol Sci Niger

  • Adeoluwa AO, Aderibigbe OA, Agboola IO, Olonode TE, Ben-Azu B. Butanol fraction of olax subscorpioidea produces antidepressant effect: evidence for the involvement of monoaminergic neurotransmission. Drug Res. © Georg Thieme Verlag KG; 2018;69:53–60.

  • Alasmari F (2020) Caffeine induces neurobehavioral effects through modulating neurotransmitters. Saudi Pharm J Elsevier 28:445–451

    Article  CAS  Google Scholar 

  • Anderson C, Dickinson DL (2010) Bargaining and trust: the effects of 36-h total sleep deprivation on socially interactive decisions. J Sleep Res 19:54–63

    Article  Google Scholar 

  • Andrade R (2011) Serotonergic regulation of neuronal excitability in the prefrontal cortex. Neuropharmacology 61:382–386

    Article  CAS  Google Scholar 

  • Ansorge MS, Zhou M, Lira A, Hen R, Gingrich JA (2004) Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science 306:879–881

    Article  CAS  Google Scholar 

  • Arrant AE, Schramm-Sapyta NL, Kuhn CM (2013) Use of the light/dark test for anxiety in adult and adolescent male rats. Behav Brain Res. NIH Public Access 256:119

  • Ashihara H, Kato M, Crozier A (2011) Distribution, biosynthesis and catabolism of methylxanthines in plants. Handb Exp Pharmacol 11–31

  • Aurora RN, Punjabi NM (2013) Obstructive sleep apnoea and type 2 diabetes mellitus: a bidirectional association. Lancet Respir Med Elsevier 1:329–338

    Article  Google Scholar 

  • Al Moutaery K, Al Deeb S, Khan HA, Tariq M (2003) Caffeine impairs short-term neurological outcome after concussive head injury in rats. Neurosurgery 53:704–712

    Article  Google Scholar 

  • Babson KA, Trainor CD, Feldner MT, Blumenthal H (2010) A test of the effects of acute sleep deprivation on general and specific self-reported anxiety and depressive symptoms: an experimental extension. J Behav Ther Exp Psychiatry 41:297–303

    Article  Google Scholar 

  • Baldwin HA, File SE (1989) Caffeine-induced anxiogenesis: the role of adenosine, benzodiazepine and noradrenergic receptors. Pharmacol Biochem Behav 32:181–186

    Article  CAS  Google Scholar 

  • Basheer R, Bauer A, Elmenhorst D, Ramesh V, McCarley RW (2007) Sleep deprivation upregulates A1 adenosine receptors in the rat basal forebrain. NeuroReport 18:1895–1899

    Article  CAS  Google Scholar 

  • Baum KT, Desai A, Field J, Miller LE, Rausch J, Beebe DW (2014) Sleep restriction worsens mood and emotion regulation in adolescents. J Child Psychol Psychiatry 55:180–190

    Article  Google Scholar 

  • Besedovsky L, Lange T, Born J (2012) Sleep and immune function. Pflugers Arch 463:121–137

    Article  CAS  Google Scholar 

  • Betteridge DJ (2000) What is oxidative stress? Metabolism 49:3–8

    Article  CAS  Google Scholar 

  • Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–8

  • Bjorvatn B, Grønli J, Hamre F, Sørensen E, Fiske E, Bjørkum AA et al (2002) Effects of sleep deprivation on extracellular serotonin in hippocampus and frontal cortex of the rat. Neuroscience 113:323–330

    Article  CAS  Google Scholar 

  • Blaise JH, Park JE, Bellas NJ, Gitchell TM, Phan V (2018) Caffeine consumption disrupts hippocampal long-term potentiation in freely behaving rats. Physiol Rep 6

  • Bodenmann S, Hohoff C, Freitag C, Deckert J, Rétey J V, Bachmann V et al (2012) Polymorphisms of ADORA2A modulate psychomotor vigilance and the effects of caffeine on neurobehavioural performance and sleep EEG after sleep deprivation. Br J Pharmacol John Wiley & Sons Ltd 165:1904–13

  • Bonnet MH, Arand DL. Level of arousal and the ability to maintain wakefulness. J Sleep Res. John Wiley & Sons, Ltd; 1999;8:247–54.

  • Botton PHS, Pochmann D, Rocha AS, Nunes F, Almeida AS, Marques DM, et al. Aged mice receiving caffeine since adulthood show distinct patterns of anxiety-related behavior. Physiol Behav. Elsevier Inc.; 2017;170:47–53.

  • Broderick P, Benjamin AB (2004) Caffeine and psychiatric symptoms: a review. J Okla State Med Assoc 97(12):538–542

    Google Scholar 

  • Broderick PJ, Benjamin AB, Dennis LW (2005) Caffeine and psychiatric medication interactions: a review. J Okla State Med Assoc 98:380–384

    Google Scholar 

  • Cappelletti S, Daria P, Sani G, Aromatario M (2015) Caffeine: cognitive and physical performance enhancer or psychoactive drug? Curr Neuropharmacol 13:71–88

    Article  CAS  Google Scholar 

  • Chen X, Zhang L, Yang D, Li C, An G, Wang J, et al. Effects of caffeine on event-related potentials and neuropsychological indices after sleep deprivation. Front Behav Neurosci. Frontiers; 2020;0:108.

  • Clark I, Landolt HP. Coffee, caffeine, and sleep: a systematic review of epidemiological studies and randomized controlled trials. Sleep Med Rev. W.B. Saunders; 2017;31:70–8.

  • Clasadonte J, Scemes E, Wang Z, Boison D, Haydon PG (2017) Connexin 43-mediated astroglial metabolic networks contribute to the regulation of the sleep-wake cycle. Neuron 95:1365-1380.e5

    Article  CAS  Google Scholar 

  • Colten HR, Altevogt BM (2006) Research I of M (US) C on SM and. National Academies Press (US), Extent and health consequences of chronic sleep loss and sleep disorders

    Google Scholar 

  • Crusio WE (2001) Genetic dissection of mouse exploratory behaviour. Behav Brain Res 125:127–132

    Article  CAS  Google Scholar 

  • Chee MWL, Chuah LYM (2008) Functional neuroimaging insights into how sleep and sleep deprivation affect memory and cognition. Curr Opin Neurol 21:417–423

    Article  Google Scholar 

  • Christian MS, Ellis APJ (2011) Examining the effects of sleep deprivation on workplace deviance: a self-regulatory perspective. Acad Manage J Academy of Management 54:913–934

    Article  Google Scholar 

  • Dietz C, Dekker M (2017) Effect of green tea phytochemicals on mood and cognition. Curr Pharm Des 23:2876–2905

    Article  CAS  Google Scholar 

  • Doran SM, Van DHPA, Dinges DF (2001) Sustained attention performance during sleep deprivation: evidence of state instability. Arch Ital Biol 139:253–267

    CAS  Google Scholar 

  • Ellman GL, Courtney KD, Andres V, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    Article  CAS  Google Scholar 

  • El Yacoubi M, Ledent C, Parmentier M, Costentin J, Vaugeois JM (2000) The anxiogenic-like effect of caffeine in two experimental procedures measuring anxiety in the mouse is not shared by selective A(2A) adenosine receptor antagonists. Psychopharmacology 148:153–163

    Article  Google Scholar 

  • Esterbauer H, Cheeseman KH (1990) Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 186:407–421

    Article  CAS  Google Scholar 

  • Friedman RC, Bigger JT, Kornfeld DS (1971) The intern and sleep loss. N Engl J Med 285:201–203

    Article  CAS  Google Scholar 

  • File SE, Hyde JRG (1979) A test of anxiety that distinguishes between the actions of benzodiazepines and those of other minor tranquilisers and of stimulants. Pharmacol Biochem Behav 11:65–69

    Article  CAS  Google Scholar 

  • Fisone G, Borgkvist A, Usiello A. Caffeine as a psychomotor stimulant: mechanism of action. Cell Mol Life Sci CMLS 2004 617. Springer; 2004;61:857–72.

  • Fuster JM (2001) The prefrontal cortex–an update: time is of the essence. Neuron 30:319–333

    Article  CAS  Google Scholar 

  • Gopalakrishnan A, Ji LL, Cirelli C (2004) Sleep deprivation and cellular responses to oxidative stress. Sleep 27:27–35

    Article  Google Scholar 

  • García-Molina A, Tirapu-Ustárroz J, Luna-Lario P, Ibáñez J (2010) Duque P [Are intelligence and executive functions the same thing?]. Rev Neurol 50:738–746

    Google Scholar 

  • Goldschmied JR, Cheng P, Kemp K, Caccamo L, Roberts J, Deldin PJ (2015) Napping to modulate frustration and impulsivity: a pilot study. Personal Individ Differ 86:164–167

    Article  Google Scholar 

  • Gilliland K, Andress D (1981) Ad lib caffeine consumption, symptoms of caffeinism, and academic performance. Am J Psychiatry 138:512–514

    Article  CAS  Google Scholar 

  • Giedke H, Schwärzler F. Therapeutic use of sleep deprivation in depression. Sleep Med Rev. W.B. Saunders; 2002;6:361–77.

  • Greden JF (1974) Anxiety or caffeinism: a diagnostic dilemma. Am J Psychiatry American Psychiatric Publishing 131:1089–1092

    CAS  Google Scholar 

  • Hansen LA, Daniel SE, Wilcock GK, Love S. Frontal cortical synaptophysin in Lewy body diseases: relation to Alzheimer’s disease and dementia. J Neurol Neurosurg Psychiatry. BMJ Publishing Group Ltd; 1998;64:653–6.

  • Hartmann J, Kiewert C, Duysen EG, Lockridge O, Greig NH, Klein J (2007) Excessive hippocampal acetylcholine levels in acetylcholinesterase-deficient mice are moderated by butyrylcholinesterase activity. J Neurochem 100:1421–1429

    Article  CAS  Google Scholar 

  • Havekes R, Vecsey CG, Abel T (2012) The impact of sleep deprivation on neuronal and glial signaling pathways important for memory and synaptic plasticity. Cell Signal 24:1251–1260

    Article  CAS  Google Scholar 

  • Hilakivi LA, Durcan MJ, Lister RG (1989) Effects of caffeine on social behavior, exploration and locomotor activity: interactions with ethanol. Life Sci Netherlands: Elsevier Science 44:543–553

    Article  CAS  Google Scholar 

  • Hipólide DC, Moreira KM, Barlow KBL, Wilson AA, Nobrega JN, Tufik S (2005) Distinct effects of sleep deprivation on binding to norepinephrine and serotonin transporters in rat brain. Prog Neuropsychopharmacol Biol Psychiatry 29:297–303

    Article  Google Scholar 

  • Högl B, Peralta C, Wetter TC, Gershanik O, Trenkwalder C. Effect of sleep deprivation on motor performance in patients with Parkinson’s disease. Mov Disord. John Wiley & Sons, Ltd; 2001;16:616–21.

  • Irwin C, Khalesi S, Desbrow B, McCartney D (2020) Effects of acute caffeine consumption following sleep loss on cognitive, physical, occupational and driving performance: a systematic review and meta-analysis. Neurosci Biobehav Rev Pergamon 108:877–888

    Article  CAS  Google Scholar 

  • Janz R, Südhof TC, Hammer RE, Unni V, Siegelbaum SA, Bolshakov VY (1999) Essential roles in synaptic plasticity for synaptogyrin I and synaptophysin I. Neuron 24:687–700

    Article  CAS  Google Scholar 

  • Kamphuis J, Meerlo P, Koolhaas JM, Lancel M (2012) Poor sleep as a potential causal factor in aggression and violence. Sleep Med Elsevier 13:327–334

    Article  Google Scholar 

  • Karcz-Kubicha M, Antoniou K, Terasmaa A, Quarta D, Solinas M, Justinova Z et al (2003) Involvement of adenosine A1 and A2A receptors in the motor effects of caffeine after its acute and chronic administration. Neuropsychopharmacol off Publ Am Coll Neuropsychopharmacol 28:1281–1291

    Article  CAS  Google Scholar 

  • Kahn-Greene ET, Killgore DB, Kamimori GH, Balkin TJ, Killgore WDS (2007) The effects of sleep deprivation on symptoms of psychopathology in healthy adults. Sleep Med 8:215–221

    Article  Google Scholar 

  • Kalsi J, Tervo T, Bachour A, Partinen M (2018) Sleep versus non − sleep-related fatal road accidents. Sleep Med Elsevier 51:148–152

    Article  Google Scholar 

  • Kim J-W, Seung H, Kwon KJ, Ko MJ, Lee EJ, Oh HA, et al. Subchronic treatment of donepezil rescues impaired social, hyperactive, and stereotypic behavior in valproic acid-induced animal model of autism. PLOS ONE. Public Library of Science; 2014;9:e104927.

  • Khadrawy YA, Nour NA, Aboul Ezz HS (2011) Effect of oxidative stress induced by paradoxical sleep deprivation on the activities of Na+, K + -ATPase and acetylcholinesterase in the cortex and hippocampus of rat. Transl Res J Lab Clin Med 157:100–107

    CAS  Google Scholar 

  • Khcharem A, Souissi M, Atheymen R, Souissi W, Sahnoun Z. Effects of caffeine ingestion on psychomotor state and oxidative stress markers after an 8-km run competition in sleep-deprived recreational runners. https://doi.org/10.1080/0929101620211925483. Taylor & Francis; 2021;

  • Khcharem A, Souissi M, Atheymen R, Mahmoud L Ben, Sahnoun Z. Effects of caffeine ingestion on 8-km run performance and cognitive function after 26 hours of sleep deprivation. https://doi.org/10.1080/0929101620201778975. Taylor & Francis; 2020;

  • Khor YM, Soga T, Parhar IS (2013) Caffeine neuroprotects against dexamethasone-induced anxiety-like behaviour in the Zebrafish (Danio rerio). Gen Comp Endocrinol 181:310–315

    Article  CAS  Google Scholar 

  • Ko BS, Ahn SH, Noh DO, Hong K-B, Han SH, Suh HJ (2017) Effect of explosion-puffed coffee on locomotor activity and behavioral patterns in Drosophila melanogaster. Food Res Int Ott Ont 100:252–260

    Article  CAS  Google Scholar 

  • Kulkarni S, Singh K, Bishnoi M. Involvement of adenosinergic receptors in anxiety related behaviours. Indian J Exp Biol. 2007;

  • Kung JC, Chen TC, Shyu BC, Hsiao S (2010) Huang ACW. Anxiety- and depressive-like responses and c-fos activity in preproenkephalin knockout mice, Oversensitivity hypothesis of enkephalin deficit-induced posttraumatic stress disorder. J Biomed Sci, p 17

    Google Scholar 

  • Lara DR (2010) Caffeine, mental health, and psychiatric disorders. J Alzheimers Dis JAD 20(Suppl 1):S239-248

    Article  CAS  Google Scholar 

  • Lanzenberger RR, Mitterhauser M, Spindelegger C, Wadsak W, Klein N, Mien L-K et al (2007) Reduced serotonin-1A receptor binding in social anxiety disorder. Biol Psychiatry 61:1081–1089

    Article  CAS  Google Scholar 

  • Lim J, Dinges DF. Sleep deprivation and vigilant attention. W Pfaff B Kieffer Eds Mol. Biophys. Mech. Arousal Alertness Atten. 2008 [cited 2021 Sep 17]. p. 305–22. Available from: https://psycnet.apa.org/record/2008-11535-027

  • López-Cruz L, Salamone JD, Correa M (2013) The impact of caffeine on the behavioral effects of ethanol related to abuse and addiction: a review of animal studies. Journal of Caffeine Research 3(1):9–21

    Article  Google Scholar 

  • López-Cruz L, Salamone JD, Correa M. Caffeine and selective adenosine receptor antagonists as new therapeutic tools for the motivational symptoms of depression. Front Pharmacol. Frontiers; 2018;0:526.

  • Mahajan K, Velaga NR. Effects of partial sleep deprivation on braking response of drivers in hazard scenarios. Accid Anal Prev. Pergamon; 2020;142:105545.

  • Martin L, Iceberg E. Quantifying social motivation in mice using operant conditioning. J Vis Exp JoVE. 2015;e53009.

  • Markram H, Toledo-Rodriguez M, Wang Y, Gupta A, Silberberg G, Wu C (2004) Interneurons of the neocortical inhibitory system. Nat Rev Neurosci 5:793–807

    Article  CAS  Google Scholar 

  • Maroteaux L, Saudou F, Amlaiky N, Boschert U, Plassat JL, Hen R (1992) Mouse 5HT1B serotonin receptor: cloning, functional expression, and localization in motor control centers. Proc Natl Acad Sci U S A 89:3020–3024

    Article  CAS  Google Scholar 

  • Meerlo P, Havekes R, Steiger A. Chronically restricted or disrupted sleep as a causal factor in the development of depression. Curr Top Behav Neurosci. Springer, Berlin, Heidelberg; 2015;25:459–81.

  • Meerlo P, Sgoifo A, Suchecki D (2008) Restricted and disrupted sleep: effects on autonomic function, neuroendocrine stress systems and stress responsivity. Sleep Med Rev 12:197–210

    Article  Google Scholar 

  • Moradi A, Nazari SSH, Rahmani K. Sleepiness and the risk of road traffic accidents: a systematic review and meta-analysis of previous studies. Transp Res Part F Traffic Psychol Behav. Pergamon; 2019;65:620–9.

  • Moy SS, Nadler JJ, Perez A, Barbaro RP, Johns JM, Magnuson TR et al (2004) sociability and preference for social novelty in five inbred strains: an approach to assess autistic-like behavior in mice. Genes Brain Behav 3:287–302

    Article  CAS  Google Scholar 

  • Murphy DL, Lesch K-P (2008) Targeting the murine serotonin transporter: insights into human neurobiology. Nat Rev Neurosci 9:85–96

    Article  CAS  Google Scholar 

  • Muzur A, Pace-Schott EF, Hobson JA (2002) The prefrontal cortex in sleep. Trends Cogn Sci 6:475–481

    Article  Google Scholar 

  • Nadal RA, Pallares, Ferré NS. The effects of caffeine in the social interaction test and on exploration in rats: comparison with ethanol and clorazepate. Behav Pharmacol. 1993;4:501–8.

  • Nih, Od, Oer, Olaw. Guide laboratory animals for the care and use of eighth edition committee for the update of the guide for the care and use of laboratory animals institute for Laboratory Animal Research Division on Earth and Life Studies. 2011.

  • Noguti J, Andersen ML, Cirelli C, Ribeiro DA (2013) Oxidative stress, cancer, and sleep deprivation: is there a logical link in this association? Sleep Breath 17:905–910

    Article  Google Scholar 

  • Ofluoglu E, Pasaoglu H, Pasaoglu A (2009) The effects of caffeine on L-arginine metabolism in the brain of rats. Neurochem Res 34:395–399

    Article  CAS  Google Scholar 

  • Onaolapo, O. J., & Onaolapo, A. Y. (2020). Caffeine, sleep, and antioxidant status. In Neurological Modulation of Sleep (pp. 265–274). Academic Press.

  • Onaolapo AY, Odetunde I, Akintola AS, Ogundeji MO, Ajao A, Obelawo AY et al (2019) Dietary composition modulates impact of food-added monosodium glutamate on behaviour, metabolic status and cerebral cortical morphology in mice. Biomed Pharmacother Biomedecine Pharmacother 109:417–428

    Article  CAS  Google Scholar 

  • Onaolapo OJ, Onaolapo AY, Akanmu MA, Olayiwola G (2015) Caffeine/sleep-deprivation interaction in mice produces complex memory effects. Ann Neurosci 22:139–149

    Article  Google Scholar 

  • Panksepp J (2010) Affective neuroscience of the emotional BrainMind: evolutionary perspectives and implications for understanding depression. Dialogues Clin Neurosci 12:533–545

    Article  Google Scholar 

  • Paiva T, Gaspar T, Matos MG. Mutual relations between sleep deprivation, sleep stealers and risk behaviours in adolescents. Sleep Sci. No longer published by Elsevier; 2016;9:7–13.

  • Penetar D, McCann U, Thorne D, Kamimori G, Galinski C, Sing H, et al. Caffeine reversal of sleep deprivation effects on alertness and mood. Psychopharmacol 1993 1122. Springer; 1993;112:359–65.

  • Peters A, Kara DA. The neuronal composition of area 17 of rat visual cortex. II. The nonpyramidal cells. J Comp Neurol. 1985;234:242–63.

  • Picciotto MR, Higley MJ, Mineur YS (2012) Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior. Neuron 76:116–129

    Article  CAS  Google Scholar 

  • Porras-Segovia A, Pérez-Rodríguez MM, López-Esteban P, Courtet P, Barrigón M ML, López-Castromán J, et al. Contribution of sleep deprivation to suicidal behaviour: a systematic review. Sleep Med Rev. W.B. Saunders; 2019;44:37–47.

  • Portas CM, Bjorvatn B, Fagerland S, Grønli J, Mundal V, Sørensen E et al (1998) On-line detection of extracellular levels of serotonin in dorsal raphe nucleus and frontal cortex over the sleep/wake cycle in the freely moving rat. Neuroscience 83:807–814

    Article  CAS  Google Scholar 

  • Portas CM, Bjorvatn B, Ursin R (2000) Serotonin and the sleep/wake cycle: special emphasis on microdialysis studies. Prog Neurobiol 60:13–35

    Article  CAS  Google Scholar 

  • Puig MV, Gulledge AT (2011) Serotonin and prefrontal cortex function: neurons, networks, and circuits. Mol Neurobiol 44:449–464

    Article  CAS  Google Scholar 

  • Prajapati SK, Dangi DS, Krishnamurthy S. Repeated caffeine administration aggravates post-traumatic stress disorder-like symptoms in rats. Physiol Behav. Elsevier; 2019;211:112666.

  • Rahal A, Kumar A, Singh V, Yadav B, Tiwari R, Chakraborty S et al (2014) Oxidative stress, prooxidants, and antioxidants: the interplay. BioMed Res Int 2014:761264

    Article  Google Scholar 

  • Ramsawh HJ, Stein MB, Belik S-L, Jacobi F, Sareen J (2009) Relationship of anxiety disorders, sleep quality, and functional impairment in a community sample. J Psychiatr Res 43:926–933

    Article  Google Scholar 

  • Reimund E (1994) The free radical flux theory of sleep. Med Hypotheses 43:231–233

    Article  CAS  Google Scholar 

  • Ribeiro JA, Sebastião AM (2010) Caffeine and adenosine. J Alzheimers Dis JAD 20(Suppl 1):S3-15

    Article  CAS  Google Scholar 

  • Richards G, Smith A (2015) Caffeine consumption and self-assessed stress, anxiety, and depression in secondary school children. J Psychopharmacol Oxf Engl 29:1236–1247

    Article  CAS  Google Scholar 

  • Ruby CL, Adams CA, Mrazek DA, Choi D-S. Adenosine signaling in anxiety [Internet]. Anxiety Disord. IntechOpen; 2011 [cited 2021 Sep 21]. Available from: https://www.intechopen.com/chapters/17570

  • Santana N, Bortolozzi A, Serrats J, Mengod G, Artigas F (1991) Expression of serotonin1A and serotonin2A receptors in pyramidal and GABAergic neurons of the rat prefrontal cortex. Cereb Cortex N Y N 2004(14):1100–1109

    Google Scholar 

  • Schneider CA, Rasband WS, Eliceiri KW. NIH image to ImageJ: 25 years of image analysis. Nat. Methods. Nat Methods; 2012. p. 671–5.

  • Simon EB, Walker M. Sleep loss causes social withdrawal and loneliness. Nat Commun. 2018;

  • Shively CA, Friedman DP, Gage HD, Bounds MC, Brown-Proctor C, Blair JB et al (2006) Behavioral depression and positron emission tomography-determined serotonin 1A receptor binding potential in cynomolgus monkeys. Arch Gen Psychiatry 63:396–403

    Article  CAS  Google Scholar 

  • Slattery DA, Cryan JF. Using the rat forced swim test to assess antidepressant-like activity in rodents. Nat Protoc 2012 76. Nature Publishing Group; 2012;7:1009–14.

  • Spriet LL (1995) Caffeine and performance. Int J Sport Nutr Exerc Metab 5(s1):S84–S99

    Article  Google Scholar 

  • Stepan ME, Altmann EM, Fenn KM (2021) Caffeine selectively mitigates cognitive deficits caused by sleep deprivation. American Psychological Association, J Exp Psychol Learn Mem Cogn

    Book  Google Scholar 

  • Sterniczuk R, Theou O, Rusak B, Rockwood K (2013) Sleep disturbance is associated with incident dementia and mortality. Curr Alzheimer Res 10:767–775

    Article  CAS  Google Scholar 

  • Swiergiel AH, Dunn AJ (2007) Effects of interleukin-1β and lipopolysaccharide on behavior of mice in the elevated plus-maze and open field tests. Pharmacol Biochem Behav Elsevier 86:651–659

    Article  CAS  Google Scholar 

  • Sze C-I, Troncoso JC, Kawas C, Mouton P, Price DL, Martin LJ (1997) Loss of the presynaptic vesicle protein synaptophysin in hippocampus correlates with cognitive decline in Alzheimer disease. J Neuropathol Exp Neurol 56:933–944

    Article  CAS  Google Scholar 

  • Szuba MP, Baxter LR, Fairbanks LA, Guze BH, Schwartz JM (1991) Effects of partial sleep deprivation on the diurnal variation of mood and motor activity in major depression. Biol Psychiatry 30:817–829

    Article  CAS  Google Scholar 

  • Tampellini D, Capetillo-Zarate E, Dumont M, Huang Z, Yu F, Lin MT et al (2010) Effects of synaptic modulation on β-amyloid, synaptophysin, and memory performance in Alzheimer’s disease transgenic mice. J Neurosci Society for Neuroscience 30:14299–14304

    Article  CAS  Google Scholar 

  • Trang A, Khandhar PB. Physiology, Acetylcholinesterase. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 [cited 2021 Sep 22]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK539735/

  • Temido-Ferreira M, Coelho JE, Pousinha PA, Lopes L V. Novel players in the aging synapse: impact on cognition. J Caffeine Adenosine Res. Mary Ann Liebert, Inc.; 2019;9:104.

  • van Duinen H, Lorist MM, Zijdewind I (2005) The effect of caffeine on cognitive task performance and motor fatigue. Psychopharmacology 180(3):539–547

    Article  CAS  Google Scholar 

  • Vargas-Garrido H, Moyano-Díaz E, Andrades K. Sleep problems are related to commuting accidents rather than to workplace accidents. BMC Public Health 2021 211. BioMed Central; 2021;21:1–7.

  • Wadhwa M, Chauhan G, Roy K, Sahu S, Deep S, Jain V, Panjwani U (2018) Caffeine and modafinil ameliorate the neuroinflammation and anxious behavior in rats during sleep deprivation by inhibiting the microglia activation. Front Cell Neurosci 12:49

    Article  Google Scholar 

  • Wang J, Zhang HY, Tang XC (2010) Huperzine a improves chronic inflammation and cognitive decline in rats with cerebral hypoperfusion. J Neurosci Res 88:807–815

    CAS  Google Scholar 

  • Walker M. Why we sleep: unlocking the power of sleep and dreams. Simon and Schuster; 2017.

  • Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc 2007 22. Nature Publishing Group; 2007;2:322–8.

  • Wess J (2003) Novel insights into muscarinic acetylcholine receptor function using gene targeting technology. Trends Pharmacol Sci 24:414–420

    Article  CAS  Google Scholar 

  • Xia J, Yang H, Mu M, Micovic N, Poskanzer KE, Monaghan JR, et al. Imaging in vivo acetylcholine release in the peripheral nervous system with a fluorescent nanosensor. Proc Natl Acad Sci [Internet]. National Academy of Sciences; 2021 [cited 2021 Sep 21];118. Available from: https://www.pnas.org/content/118/14/e2023807118

  • Yan Z, Rein B. Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications. Mol Psychiatry 2021. Nature Publishing Group; 2021;1–21.

  • Zagaar M, Dao A, Levine A, Alhaider I, Alkadhi K (2013) Regular exercise prevents sleep deprivation associated impairment of long-term memory and synaptic plasticity in the CA1 area of the hippocampus. Sleep 36:751–761

    Article  Google Scholar 

  • Zielinski MR, McKenna JT, McCarley RW (2016) Functions and mechanisms of sleep. AIMS Neurosci 3:67–104

    Article  Google Scholar 

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Authors and Affiliations

  1. Neuroscience Unit, Department of Human Anatomy, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria

    Edem Ekpenyong Edem, Uyi Emmanuel Okhonmina, Kate Eberechukwu Nebo, Adedamola Adediran Fafure & Mujeeb Adekunle Adedokun

  2. Neuropharmacology Unit, Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria

    Elizabeth Toyin Akinluyi

  3. Department of Anatomy, College of Medicine, University of Lagos, Idi-Araba, Lagos State, Nigeria

    Edem Ekpenyong Edem & Daniel Akinwale Ikuelogbon

  4. Department of Medical Biochemistry, College of Medicine and Health Sciences, Afe Babalola University, Ekiti State, Ado-Ekiti, Nigeria

    Ayodeji Augustine Olabiyi

Authors
  1. Edem Ekpenyong Edem
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  2. Uyi Emmanuel Okhonmina
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  3. Kate Eberechukwu Nebo
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  4. Elizabeth Toyin Akinluyi
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  5. Daniel Akinwale Ikuelogbon
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  6. Adedamola Adediran Fafure
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  7. Ayodeji Augustine Olabiyi
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  8. Mujeeb Adekunle Adedokun
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Contributions

Edem Ekpenyong Edem conceived and designed the study, provided research materials, and supervised the study. Uyi Emmanuel Okhonmina conducted research, provided research materials, collected, and organized data. Kate Eberechukwu Nebo and Elizabeth Toyin Akinluyi analysed and interpreted data. Daniel Akinwale Ikuelogbon conducted research and developed first draft of the manuscript. Adedamola Adediran Fafure, Ayodeji Augustine Olabiyi, and Mujeeb Adekunle Adedokun shared in the experimental work, collected data, and reviewed manuscript. All authors have critically reviewed and approved the final draft and are responsible for the content and similarity index of the manuscript.

Corresponding author

Correspondence to Edem Ekpenyong Edem.

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Ethical Approval

The study was approved by the Research Committee on Animal Use and Experimentation of Afe Babalola University, Nigeria (AB/EC/19/10/15).

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The authors declare no competing interests.

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Edem, E.E., Okhonmina, U.E., Nebo, K.E. et al. Combined Exposure to Chronic Sleep Deprivation and Caffeine Potentiates Behavioural Deficits by Altering Neurochemical Profile and Synaptophysin Expression in Long-Evans Rats. Neurotox Res 40, 2001–2015 (2022). https://doi.org/10.1007/s12640-022-00589-1

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