Issue

Vol. 65 No. 2: Issue 2

The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.

Caffeine as a potential arousal enhancer: altered NMDA subunit gene expression without improving cognitive performance in REM sleep deprived rats

https://doi.org/10.14715/cmb/2019.65.2.10
Leyla Sahin
Department of Physiology, Faculty of Medicine, Mersin University, Mersin, Turkey
Ozge Selin Cevik
Department of Physiology, Faculty of Medicine, Mersin University, Mersin, Turkey
Dilan Deniz Koyuncu
Department of Physiology, Faculty of Medicine, Mersin University, Mersin, Turkey
Sayad Kocahan
Department of Physiology, Faculty of Medicine, Adıyaman University, Adıyaman, Turkey

Corresponding Author(s) : Leyla Sahin

leyladrm@gmail.com

Cellular and Molecular Biology, Vol. 65 No. 2: Issue 2

Abstract

Caffeine is one of the most extensively consumed stimulants in the world and has been suggested to induce wakefulness by antagonizing the function of the adenosine A2A receptor. Therefore, we investigated the effects of chronic caffeine consumption on learning and memory in the REM sleep-deprived rats.Male Wistar rats (n = 50), were randomly assigned into 5 groups: Control (C), Caffeine (Cf), Pedestal Control (PC), Sleep Deprivation (SD), Sleep Deprivation and Caffeine (SD + Cf). Sleep deprivation procedure was applied as the flower-pot technique. SD and SD + Cf groups were deprived for 18 hours in a day for 21 days. Caffeine was administered daily in drinking water (0.3 gâ„L) for 5 weeks. For evaluated learning and memory function, Morris Water Maze Test (MWM) was used. Fluidigm Access Array was used for Grin2a, Grin2b, BDNF, cdk5/cdk5r1, CaMKIIa genes expression in the hippocampus. Distance moved and escape latency were decreased through trial days (p<0.05). However, there is no significant difference between groups for time spent in targeted quadrant during probe test for memory performance. Grin2a up-regulation was found in Cf and SD+Cf (p<0.05), and cdk5r1 increased in Cf and PC control (p<0.05). Also, BDNF up-regulation was found in PC group. Grin2b, Cdk5, CaMKIIa expression levels were not changed significantly. We showed chronic caffeine altered some of the hippocampal genes without changing learning and memory in REM sleep deprived rats. Chronic consumption of caffeine caused up-regulation in Grin2a that subunit of NMDA receptor. We supposed that chronic caffeine consumption maintained arousal without affecting learning and memory performance.

Keywords

Caffeine CaMKIIa MWMT NMDA receptors REM-sleep deprivation.
Sahin, L., Cevik, O. S., Koyuncu, D. D., & Kocahan, S. (2019). Caffeine as a potential arousal enhancer: altered NMDA subunit gene expression without improving cognitive performance in REM sleep deprived rats. Cellular and Molecular Biology, 65(2), 63–68. https://doi.org/10.14715/cmb/2019.65.2.10
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. Stickgold R. Sleep-dependent memory consolidation. Nature 2005; 437: 1272-8.
  2. Dos Santos AC, Castro MA, Jose EA, Delattre AM, Dombrowski PA, Da Cunha C, et al. REM sleep deprivation generates cognitive and neurochemical disruptions in the intranigral rotenone model of Parkinson's disease. J Neurosci Res 2013; 911: 508-16.
  3. Proenca MB, Dombrowski PA, Da Cunha C, Fischer L, Ferraz AC, Lima MM. Dopaminergic D2 receptor is a key player in the substantia nigra pars compacta neuronal activation mediated by REM sleep deprivation. Neuropharmacology 2014; 761:18-26.
  4. Smith C. Sleep states and memory processes. Behav Brain Res 1995; 69: 137-45.
  5. Stone MJ. Memory performance after arousal from different sleep stages. Br J Psychol 1977; 681: 77-81.
  6. Ferre S. An update on the mechanisms of the psychostimulant effects of caffeine. J. Neurochem 2008; 105: 1067-79.
  7. Kim EY, Mahmoud GS, Grover LM. REM sleep deprivation inhibits LTP in vivo in area CA1 of rat hippocampus. Neurosci Lett 2005; 388: 163-7.
  8. Polzella DJ. Effects of sleep deprivation on short-term recognition memory. Journal of experimental psychology. Exp Psychol Hum Learn 1975: 104; 194-200.
  9. Dall'Igna OP, Souza DO, Lara DR. Caffeine as a neuroprotective adenosine receptor antagonist. Ann Pharmacother 2004: 387; 17-8.
  10. Kopf SR, Melani A, Pedata F, Pepeu G. Adenosine and memory storage: effect of A(1) and A(2) receptor antagonists. Psychopharmacology 1999: 146; 214-9.
  11. De Mendonca A, Sebastiao AM, Ribeiro JA. Inhibition of NMDA receptor-mediated currents in isolated rat hippocampal neurones by adenosine A1 receptor activation. Neuroreport 1995: 6; 1097-100.
  12. Dunwiddie TV, Masino SA. The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci 2001: 243; 1-55.
  13. Alhaider IA, Aleisa AM, Tran TT, Alzoubi KH, Alkadhi KA. Chronic caffeine treatment prevents sleep deprivation-induced impairment of cognitive function and synaptic plasticity. Sleep 2010: 33; 437-44.
  14. Sahu S, Kauser H, Ray K, Kishore K, Kumar S, Panjwani U. Caffeine and modafinil promote adult neuronal cell proliferation during 48 h of total sleep deprivation in rat dentate gyrus. Exp Neurol 2013: 248; 470-81.
  15. Tsai LH, Delalle I, Caviness VS, Jr Chae T, Harlow E. p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5. Nature 1994: 317; 419-23
  16. Kawauchi T. Cdk5 regulates multiple cellular events in neural development, function and disease. Dev Growth Differ 2014: 56; 335-48.
  17. Plattner F, Hernández A, Kistler TM, Pozo K, Zhong P, Yuen EY, Guo, A. Memory enhancement by targeting Cdk5 regulation of NR2B. Neuron 2014: 8; 1070-83.
  18. Alhaider IA, Aleisa AM, Tran TT, Alkadhi KA. Sleep deprivation prevents stimulation-induced increases of levels of P-CREB and BDNF: protection by caffeine. Mol Cell Neurosci 2011: 46; 742-51.
  19. Costa MS, Botton PH, Mioranzza S, Ardais AP, Moreira JD, Souza DO, et al. Caffeine improves adult mice performance in the object recognition task and increases BDNF and TrkB independent on phospho-CREB immunocontent in the hippocampus. Neurochem Int 2008: 53; 89-94.
  20. Süer C, Dolu N, Artis AS, Sahin L, Yilmaz A, Cetin A. The effects of long-term sleep deprivation on the long-term potentiation in the dentate gyrus and brain oxidation status in rats. Neurosci Res 2011: 70; 71-77.
  21. Akillioglu K, Babar Melik E, Melik E, Kocahan S. The investigation of neonatal MK-801 administration and physical environmental enrichment on emotional and cognitive functions in adult Balb/c mice. Pharmacol Biochem Behav 2012: 102; 407-14.
  22. Ancoli-Israel S. Sleep and aging: prevalence of disturbed sleep and treatment considerations in older adults. J Clin Psychiatry 2005: 66; 24-30.
  23. Xie M, Yan J, He C, Yang L, Tan G, Li C, et al. Short-term sleep deprivation impairs spatial working memory and modulates expression levels of ionotropic glutamate receptor subunits in hippocampus. Behav Brain Res 2015: 286; 64-70.
  24. Alhaider IA, Aleisa AM, Tran TT, Alkadhi KA. Caffeine prevents sleep loss-induced deficits in long-term potentiation and related signaling molecules in the dentate gyrus. Eur J Neurosci 2010: 311; 368-76.
  25. Samkoff JS, Jacques CH. A review of studies concerning effects of sleep deprivation and fatigue on residents' performance. Acad Med 1991: 66; 687-93.
  26. Cevik OS, Sahin L,Tamer L. Long term treadmill exercise performed to chronic social isolated rats regulate anxiety behavior without improving learning. Life Sci J 2018: 200; 126-133
  27. Angelucci ME, Cesario C, Hiroi RH, Rosalen PL, Da Cunha C. Effects of caffeine on learning and memory in rats tested in the Morris water maze. Braz J Med Biol Res 2002: 351; 201-8.
  28. Souissi M, Chtourou H, Abedelmalek S, Ghozlane IB, Sahnoun Z. The effects of caffeine ingestion on the reaction time and short-term maximal performance after 36 h of sleep deprivation. Physiol Behav 2014: 13; 11-6.
  29. Wadhwa M, Sahu S, Kumari P, Kauser H, Ray K, Panjwani U. Caffeine and modafinil given during 48 h sleep deprivation modulate object recognition memory and synaptic proteins in the hippocampus of the rat. Behav Brain Res 2015: 294; 95-101.
  30. Stickgold R, James L, Hobson JA. Visual discrimination learning requires sleep after training. Nature Neurosci 2003: 121; 237.
  31. Cunha RA, Agostinho PM. Chronic caffeine consumption prevents memory disturbance in different animal models of memory decline. J Alzheimers Dis 2010: 20; 95-116.
  32. Huang ZL, Qu WM, Eguchi N, Chen JF, Schwarzschild MA, Fredholm BB, et al. Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Nature Neurosci 2005: 88; 58-9.
  33. Hildebrand ME, Xu J, Dedek A, Li Y, Sengar AS, Beggs S, Salter MW. Potentiation of synaptic GluN2B NMDAR currents by Fyn kinase is gated through BDNF-mediated disinhibition in spinal pain processing. Cell Rep 2016: 17; 2753-2765.
  34. Mishiba T, Tanaka M, Mita N, He X, Sasamoto K, Itohara S, Ohshima T. Cdk5/p35 functions as a crucial regulator of spatial learning and memory. Mol Brain 2014: 7; 82.
  35. Noriega NC, Garyfallou VT, Kohama SG, Urbanski HF. Glutamate receptor subunit expression in the rhesus macaque locus coeruleus. Brain Res 2007: 11; 53-65.
  36. Brann DW, Mahesh VB, Glutamate: a major neuroendocrine excitatory signal mediating steroid effects on gonadotropin secretion. J Steroid Biochem Mol Biol 1995: 53; 325–329.
  37. Walling SG, Harley CW. Locus ceruleus activation initiates delayed synaptic potentiation of perforant path input to the dentate gyrus in awake rats: a novel β-adrenergic-and protein synthesis-dependent mammalian plasticity mechanism. J Neurosci 2004: 24; 598-604.
  38. Simon DK, Wu C, Tilley BC, Lohmann K, Klein C, Payami H, Hauser RA. Caffeine, creatine, GRIN2A and Parkinson's disease progression. J Neurol Sci 2017: 375; 355-359.
  39. Schwarzschild MA, Xu K, Oztas E, Petzer JP, Castagnoli K, Castagnoli N, Chen JF. Neuroprotection by caffeine and more specific A2A receptor antagonists in animal models of Parkinson's disease. Neurology 2003: 61; 55–61.
  40. Kachroo A, Irizarry MC, Schwarzschild MA. Caffeine protects against combined paraquat and maneb-induced dopaminergic neuron degeneration. Exp Neurol 2010: 223; 657–661.
  41. Kachroo MA, Schwarzschild MA. Adenosine A2A receptor gene disruption protects in an alpha-synuclein model of Parkinson's disease. Ann Neurol 2012: 71; 278–282.
Read More
Author biographies is not available.
Crossref
Scopus
Google Scholar
Europe PMC
Download this PDF file
PDF
Statistic
Read Counter : 1113 Download : 527