Effect of caffeine supplementation during treadmill exercise on hippocampal genes expression levels in adolescent rats

Year 2023, Volume: 9 Issue: 2, 348 - 358, 04.03.2023

Fatma Bakır , Özge Selin Çevik , Seval Müsüroğlu Keloğlan , Leyla Şahin

https://doi.org/10.18621/eurj.1241667

Cited By: 1

Abstract

Objectives: The usage of caffeine, a psychostimulant that is included in many foods and drinks, is rising, especially among young people. Also, caffeine works as an ergogenic substance during exercise to improve performance, and strength. In this study, our aim was to investigate the effect of caffeine consumption and exercise on hippocampal learning and memory functions in early life.

Methods: Postnatal 28 days old Wistar albino male rats (n = 28) were randomly divided into 4 groups; control group (C), caffeine group (Cf), exercise group (E), caffeine+exercise group (CfE). Caffeine was dissolved in drinking water (0.3 g/L) and the treadmill exercise was applied 3 days a week. Following, the rats were applied to Morris Water Maze Test (MWMT) and open field test. N-methyl-D-aspartate (NMDA) receptors NR2A, NR2B, and brain-derived neurotrophic factor (BDNF) gene expression levels were investigated in hippocampus tissue by RT-PCR.

Results: In MWMT, there was no significant difference in terms of learning and memory functions and hippocampal gene expression levels of the groups (p > 0.05). In the open field test, the time spent in the center was decreased in the CfE group, and the number of entries to the center was decreased in the E and CfE groups compared to the control group (p < 0.05).

Conclusions: We assumed that caffeine given with exercise application caused anxiety behavior but did not affect learning and memory. There is a need for new studies investigating the effect of caffeine on exercise with different doses and durations depending on age.

Keywords

Caffeine, exercise, hippocampus, learning, memory

References

• 1. Barry RJ, Rushby JA, Wallace M, Clarke AR, Johnstone SJ, Zlojutro I. Caffeine effects on resting-state arousal. Clin Neurophysiol 2005;116:2693-700.
• 2. Bonita JS, Mandarano M, Shuta D, Vinson J. Coffee and cardiovascular disease: invitro, cellular, animal, and human studies. Pharmacol Res 2007;55:187-98.
• 3. Mitchell DC, Knight CA, Hockenberry J, Teplansky R, Hartman TJ. Beverage caffeine intakes in the U.S. Food Chem Toxicol 2013;63:136-42.
• 4. Alhaider IA, Alkadhi KA. Caffeine treatment prevents rapid eye movement sleep deprivation-induced impairment of late-phase long-term potentiation in the dentate gyrus. Eur J Neurosci 2015;42:2843-50.
• 5. Oliveira RV, Dall'Igna OP, Tort AB, Schuh JF, Neto PF, Santos Gomes MW, et al. Effect of subchronic caffeine treatment on MK-801-induced changes in locomotion, cognition and ataxia in mice. Behav Pharmacol 2005;16:79-84.
• 6. Sun YL, Wang J, Yao JX, Ji CS, Dai Q, Jin YH. Physical exercise and mental health: cognition, anxiety, depression and self-concept. Sheng Li Ke Xue Jin Zhan 2014;45:337-42.
• 7. Türkiye Endokrinoloji ve Metabolizma Derneği (TEMD)-2020. Tıbbi beslenme ve egzersiz metabolizması kılavuzu. 2021. Available at: https://file.temd.org.tr/Uploads/publications/guides/documents/20210104143105-2021tbl_kilavuzada2d60e7b.pdf. Accessed January 23, 2023.
• 8. Collins A, Hill LE, Chandramohan Y, Whitcomb D, Droste SK, Reul JM. Exercise improves cognitive responses to psychological stress through enhancement of epigenetic mechanisms and gene expression in the dentate gyrus. PLoS One 2009;4:e4330.
• 9. Park JK, Lee SJ, Kim TW. Treadmill exercise enhances NMDA receptor expression in schizophrenia mice. J Exerc Rehabil 2014;10:15-21.
• 10. Dietrich MO, Mantese CE, Porciuncula LO, Ghisleni G, Vinade L, Souza DO, et al. Exercise affects glutamate receptors in postsynaptic densities from cortical mice brain. Brain Res 2005;1065:20-5.
• 11. Zhang L, Qin Z, Sharmin F, Lin W, Ricke KM, Zasloff MA, et al. Tyrosine phosphatase PTP1B impairs presynaptic NMDA receptor-mediated plasticity in a mouse model of Alzheimer's disease. Neurobiol Dis 2021;156:105402.
• 12. Leal G, Afonso PM, Salazar IL, Duarte CB. Regulation of hippocampal synaptic plasticity by BDNF. Brain Res 2015;1621:82-101.
• 13. Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci 2002;25:295-301.
• 14. Loprinzi PD, Frith EA. Brief primer on the mediational role of BDNF in the exercise-memory link. Clin Physiol Func Imaging 2019;39:9-14.
• 15. Ganio MS, Klau JF, Casa DJ, Armstrong LE, Maresh CM. Effect of caffeine on sport-specific endurance performance: a systematic review. J Strength Cond Res 2009;23:315-24.
• 16. Tunnicliffe JM, Erdman KA, Reimer RA, Lun V, Shearer J. Consumption of dietary caffeine and coffee in physically active populations: physiological interactions. Appl Physiol Nutr Metab 2008;33:1301-10.
• 17. França AP, Schamne MG, Souza BS, Luz Scheffer D, Bernardelli AK, Corrêa T, et al. Caffeine consumption plus physical exercise improves behavioral impairments and stimulates neuroplasticity in spontaneously hypertensive rats (SHR): an animal model of attention deficit hyperactivity disorder. Mol Neuro 2020;57:3902-19.
• 18. Metro D, Cernaro V, Santoro D, Papa M, Buemi M, Benvenga S, et al. Beneficial effects of oral pure caffeine on oxidative stress. J Clin Trans Endocrinol 2017;10:22-7.
• 19. Keloglan SM, Sahin L, Cevik OS. Chronic caffeine consumption improves the acute sleep deprivation-induced spatial memory impairment while altering N-methyl-D-aspartate receptor subunit expression in male rats. Int J Dev Neurosci 2022;82:596-605.
• 20. Han ME, Park KH, Baek SY, Kim BS, Kim JB, Kim HJ, et al. Inhibitory effects of caffeine on hippocampal neurogenesis and function. Biochem Biophys Res Commun 2007;356:976-80.
• 21. Batista DF, Gonçalves AF, Rafacho BP, Okoshi K, Paiva SAR, Zornoff LAM. Delayed rather than early exercise training attenuates ventricular remodeling after myocardial infarction. Int J Cardiol 2013;170:3-4.
• 22. Küçük A, Gölgeli A. [Anxiety models in experimental animals and evaluation of anxiety]. Sağlık Bilim Derg 2005;14:209-17. [Article in Turkish]
• 23. Li C, Liu Y, Yin S, Lu C, Liu D, Jiang H, et al. Long-term effects of early adolescent stress: dysregulation of hypothalamic-pituitary-adrenal axis and central corticotropin releasing factor receptor 1 expression in adult male rats. Behav Brain Res 2015;288:39-49.
• 24. Harpaz E, Tamir S, Weinstein A, Weinstein Y. The effect of caffeine on energy balance. J Basic Clin Physiol Pharmacol 2017;28:1-10.
• 25. Panchal SK, Wong WY, Kauter K, Ward LC, Brown L. Caffeine attenuates metabolic syndrome in diet-induced obese rats. Basic Nutr Invest 2012;28:1055-62.
• 26. Moy GA, McNay EC. Caffeine prevents weight gain and cognitive impairment caused by a high-fat diet while elevating hippocampal BDNF. Physiol Behav 2013;109:69-74.
• 27. Pettenuzzo LF, Noschang C, Toigo EP, Fachin A, Vendite D, Dalmaz C. Effects of chronic administration of caffeine and stress on feeding behavior of rats. Physiol Behav 2008;95:295-301.
• 28. Temple JL, Ziegler AM. Gender differences in subjective and physiological responses to caffeine and the role of steroid hormones. J Caffeine Res 2011;1:41-48.
• 29. Moore RHS, Franko DL, Thompson D, Barton B, Schreiber GB, Daniels SR. Caffeine intake in eating disorders. J Eat Disord 2006;39:162-5.
• 30. Sweney P, Levack R, Watters J, Xu Z, Yang Y. Caffeine increases food intake while reducing anxiety-related behaviors. Appetite 2016;101:171-7.
• 31. Correa M, Miguel NS, Lopez-Cruz L, Carratala-Ros C, Olivaras-Garcia R, Salamone JD. Caffeine modulates food ıntake depending on the context that gives access to food: comparison with dopamine depletion. Front Psychiatry 2018;9:411.
• 32. Smith A. Effects of caffeine on human behavior. Food Chem Toxicol 2002;40:1243-55.
• 33. Loke WH. Effects of caffeine on mood and memory. Physiol Behav 1988;44:367-72.
• 34. Traxler PA, Saho RJ, Wistner MB. The acute effects of caffeine on reaction time, memory performance, and reaction time. Onu Student Res Colloquium 2022;43.
• 35. Terry WS, Phifer B. Caffeine and memory performance on the AVLT. Psychodynamics and Psychopathology. J Clin Phychol 1986;42:863-3.
• 36. Singh AB, Xu Y, Wang H, Kumar VHS. The beneficial effects of postnatal caffeine on spatial learning in adult mice J Caffeine Adenosine Res 2009;9:64-8.
• 37. Li Y, Zhang W, Shi R, Sun M, Zhang L, Li Na, et al. Prenatal caffeine damaged learning and memory in rat offspring mediated by ARs/PKA/CREB/BDNF pathway. Physiol Res 2018;67:975-83.
• 38. Turgeon SM, Townsend SE, Dixon RS, Hickman ET, Lee SM. Chronic caffeine produces sexually dimorphic effects on amphetamine-induced behavior, anxiety and depressive-like behavior in adolescent rats. Pharmacol Biochem Behav 2016;143:26-33.
• 39. Angelucci MEM, Cesário C, Hiroi RH, Rosalen PL, Cunha CD. Effects of caffeine on learning and memory in rats tested in the Morris water maze. Braz J Med Biol Res 2002;35:1201-8.
• 40. Praag H, Shubert T, Zhao C, Gage FH. Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 2005;25:8680-5.
• 41. Grace L, Hescham S, Kellaway LA, Bugarith K, Russsell VA. Effect of exercise on learning and memory in a rat model of developmental stress. Metab Brain Dis 2009;24:643-57.
• 42. Alaei HA, Moloudi R, Sarkaki AR. Effects of treadmill running on mid-term memory and swim speed in the rat with Morris water maze test. J Bodyw Mov Ther 2008;12:72-5.
• 43. Albeck DS, Sano K, Prewit GE, Dalton L. Mild forced treadmill exercise enhances spatial learning in the aged rat. Behav Brain Res 2006;168:345-8.
• 44. Wang XQ, Wang WG. Effects of treadmill exercise intensity on spatial working memory and long-term memory in rats. Life Sci 2016;149:96-103.
• 45. Hogervorst E, Bandelow S, Schmitt J, Jentjens R, Oliveira M, Allgrove J, et al. Caffeine improves physical and cognitive performance during exhaustive exercise. Med Sci Sports Exerc 2008;40:1841-51.
• 46. Brown BA, Frost N, Rainey-Smith SR, Doecke J, Markovic S, Gordon N, et al. High-intensity exercise and cognitive function in cognitively normal older adults: a pilot randomised clinical trial. Alzheimers Res Ther 2021;13:33.
• 47. Prut I, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol 2003;463:3-33.
• 48. Ardais AP, Borges MF, Rocha AS, Sallaberry C, Cunha RA, Porciuncula LO. Caffeine triggers behavioral and neurochemical alterations in adolescent rats. Neurosci 2014;270:27-39.
• 49. Childs E, Hohoff , Deckert J, Xu K, Badner J, Wit H. Association between ADORA2A and DRD2 polymorphisms and caffeine-induced anxiety. Neuropsychopharmacol 2008;33:2791-800.
• 50. Klevebrant L, Frick A. Effects of caffeine on anxiety and panic attacks in patients with panic disorder: a systematic review and meta-analysis. Gen Hosp Psychiatry 2022;74:22-31.
• 51. Anderson NL, Hughes N. Increased emotional reactivity in rats following exposure to caffeine during adolescence. Neurotoxicol Teratol 2008;30:195-201.
• 52. Seo JH. Treadmill exercise alleviates stress-induced anxiety-like behaviors in rats. J Exerc Rehabil 2018;14:724-30.
• 53. Patki G, Li L, Allam F, Solanki N, Dao AT, Alkadhi K, et al. Moderate treadmill exercise rescues anxiety and depression-like behavior as well as memory impairment in a rat model of posttraumatic stress disorder. Physiol Behav 2014;130:47-53.
• 54. Jones AB, Gupton R, Curtis KS. Estrogen and voluntary exercise interact to attenuate stress-induced corticosterone release but not anxiety-like behaviors in female rats. Behav Brain Res 2016;311:279-86.
• 55. Hansen KB, Yi F, Perszyk RE, Furukawa H, Wollmuth LP, Gibb AJ, et al. Structure, function, and allosteric modulation of NMDA receptors. J Gen Physiol 2018;150:1081-105.
• 56. Cognato GP, Agostinho PM, Hockemeyer J, Müller CE, Souza DO, Cunha RA. Caffeine and an adenosine A(2A) receptor antagonist prevent memory impairment and synaptotoxicity in adult rats triggered by a convulsive episode in early life. J Neurochem 2010;112:453-62.
• 57. Sukhotina IA, Zvartau EE, Danysz W, Bespalov AY. Caffeine withdrawal syndrome in social interaction test in mice: effects of the NMDA receptor channel blockers, memantine and neramexane. Behav Pharmacol 2004;15:207-14.
• 58. Powel KR, Holtzman SG. Lack of NMDA receptor involvement in caffeine-induced locomotor stimulation and tolerance in rats. Pharmacol Biochem Behav 1998;59:433-8.
• 59. Yu Q, Li X, Wang J, Li Y. Effect of exercise training on long term potentiation and NMDA receptor channels in rats with cerebral infarction. Exp Ther Med 2013;6:1431-6.
• 60. Ke Z, Hu S, Cui W, Sun J, Zhang S, Mak S, et al. Bis(propyl)-cognitin potentiates rehabilitation of treadmill exercise after a transient focal cerebral ischemia, possibly via inhibiting NMDA receptor and regulating VEGF expression. Neurochem Int 2019;128:143-53.
• 61. Şahin L, Çevik SÖ, Koyuncu DD, Kocahan S. Caffeine as a potential arousal enhancer: altered NMDA subunit gene expression without improving cognitive performance in REM sleep deprived rats. Cell Mol Biol 2019;65:63-8.
• 62. Masrour FF, Peeri M, Azarbayjani M, Hosseini MJ. Voluntary exercise during adolescence mitigated negative the effects of maternal separation stress on the depressive-like behaviors of adult male rats: role of NMDA receptors. Neurochem Res 2018;43:1067-1074.
• 63. Kitamura T, Mishina M, Sugiyama H. Enhancement of neurogenesis by running wheel exercises is suppressed in mice lacking NMDA receptor epsilon 1 subunit. J Neurosci Res 2003;47:55-63.
• 64. 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.
• 65. Sallaberry C, Nunes F, Costa MS, Fioreze GT, Ardais AP, Botton PHS, et al. Chronic caffeine prevents changes in inhibitory avoidance memory and hippocampal BDNF immunocontent in middle-aged rats. Neuropharmacol 2012;64:153-9.
• 66. Soya H, Nakamura T, Deocaris CC, Kimpara A, Iimura M, Fujikawa T, et al. BDNF induction with mild exercise in the rat hippocampus. Biochem Biophys Res Commun 2007;358:961-7.
• 67. Akhavan MM, Gorji HM, Abarghoie ME, Safari M, Moghaddam BS, Vafaei AA, et al. Maternal voluntary exercise during pregnancy enhances the spatial learning acquisition but not the retention of memory in rat pups via a TrkB-mediated mechanism: the role of hippocampal BDNF expression. Iran J Basic Med Sci 2013;16:955-61.
• 68. Cechetti F, Fochesatto C, Scopel D, Nardin P, Gonçalves CA, Netto CA, et al. Effect of a neuroprotective exercise protocol on oxidative state and BDNF levels in the rat hippocampus. Brain Res 2008;1188:182-8.