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Caffeine Neuroprotection Decreases A2A Adenosine Receptor Content in Aged Mice

  • Michelle Lima Garcez
  • Adriani Paganini Damiani
  • Robson Pacheco
  • Lucas Rodrigues
  • Larissa Letieli de Abreu
  • Márcio Correa Alves
  • Vanessa Moraes de Andrade
  • Carina Rodrigues Boeck
Original Paper
  • 43 Downloads

Abstract

Caffeine is a bioactive compound worldwide consumed with effect into the brain. Part of its action in reducing incidence or delaying Alzheimer’s and Parkinson’s diseases symptoms in human is credited to the adenosine receptors properties. However, the impact of caffeine consumption during aging on survival of brain cells remains debatable. This work, we investigated the effect of low-dose of caffeine on the ectonucleotidase activities, adenosine receptors content, and paying particular attention to its pro-survival effect during aging. Male young adult and aged Swiss mice drank water or caffeine (0.3 g/L) ad libitum for 4 weeks. The results showed that long-term caffeine treatment did not unchanged ATP, ADP or AMP hydrolysis in hippocampus when compared to the mice drank water. Nevertheless, the ATP/ADP hydrolysis ratio was higher in young adult (3:1) compared to the aged (1:1) animals regardless of treatment. The content of A1 receptors did not change in any groups of mice, but the content of A2A receptors was reduced in hippocampus of mice that consumed caffeine. Moreover, the cell viability results indicated that aged mice not only had increased pyknotic neurons in the hippocampus but also had reduced damage after caffeine treatment. Overall, these findings indicate a potential neuroprotective effect of caffeine during aging through the adenosinergic system.

Keywords

Aging Adenosine receptors Caffeine Ecto-NTPDase Ecto-5′-nucleotidase 

Notes

Acknowledgements

We thank Dr. Izabel Cristina Custodio de Souza (Department of Social Medical Studies, Federal University of Pelotas, Rio Grande do Sul, Brazil), Luis Augusto Xavier Cruz, Luis Otávio Lobo Centeno, Eliane Freire Anthonisen (Department of Morphology, Institute of Biology, Federal University of Pelotas, Rio Grande do Sul, Brazil) and Cláudio Teodoro de Souza (Universidade do Extremo Sul Catarinense) for important contributions to the paper. This study was supported by Universidade do Extremo Sul Catarinense (VMA and CB).

Author Contributions

MLG: contributions to the conception of the work, acquisition, analysis and interpretation of data for the work; writing and correcting the work; final approval of the version to be published; APD, RP, LR, LLA, MCA: substantial contributions to the acquisition and analysis of data for the work; drafting the work; final approval of the version to be published; VMA: design of study; analysis and interpretation of data; correction of final version of manuscript; supervisor of APD. CRB: conception and design of study; project for funding support; analysis and interpretation of data; writing and correcting of final version of manuscript of manuscript; supervisor of the majority of post-graduation and undergraduation students. The present work was part of Dissertations of MLG. All authors—agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Compliance with Ethical Standards

Disclosure

The authors declare that there is no conflict of interests regarding the publication of this paper.

Ethical Approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The project was approved by the ethical committee of the Universidade do Extremo Sul Catarinense (n° 103/2012) and performed according recommendations for animal care on NIH Guide for Care and Use of Laboratory Animals and National Council for the Control of Animal Experimentation (CONCEA, Brazil).

References

  1. 1.
    Fredholm BB, Bättig K, Holmén J et al (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 51:83–133Google Scholar
  2. 2.
    Sonsalla PK, Wong LY, Harris SL et al (2012) Delayed caffeine treatment prevents nigral dopamine neuron loss in a progressive rat model of Parkinson’s disease. Exp Neurol 234:482–487.  https://doi.org/10.1016/j.expneurol.2012.01.022 CrossRefGoogle Scholar
  3. 3.
    Dall’Igna OP, Porciúncula LO, Souza DO et al (2003) Neuroprotection by caffeine and adenosine A2A receptor blockade of beta-amyloid neurotoxicity. Br J Pharmacol 138:1207–1209.  https://doi.org/10.1038/sj.bjp.0705185 CrossRefGoogle Scholar
  4. 4.
    Phillis JW (1995) The effects of selective A1 and A2a adenosine receptor antagonists on cerebral ischemic injury in the gerbil. Brain Res 705:79–84.  https://doi.org/10.1016/0006-8993(95)01153-6 CrossRefGoogle Scholar
  5. 5.
    El Yacoubi M, Ledent C, Ménard JF et al (2000) The stimulant effects of caffeine on locomotor behaviour in mice are mediated through its blockade of adenosine A(2A) receptors. Br J Pharmacol 129:1465–1473.  https://doi.org/10.1038/sj.bjp.0703170 CrossRefGoogle Scholar
  6. 6.
    Hoehn K, White TD (1990) Role of excitatory amino acid receptors in K+- and glutamate-evoked release of endogenous adenosine from rat cortical slices. J Neurochem 54:256–265CrossRefGoogle Scholar
  7. 7.
    Zimmermann H (1999) Two novel families of ectonucleotidases: molecular structures, catalytic properties and a search for function. Trends Pharmacol Sci 20:231–236.  https://doi.org/10.1016/S0165-6147(99)01293-6 CrossRefGoogle Scholar
  8. 8.
    Robson SC, Sévigny J, Zimmermann H (2006) The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significance. Purinergic Signal 2:409–430.  https://doi.org/10.1007/s11302-006-9003-5 CrossRefGoogle Scholar
  9. 9.
    Ciruela F, Casadó V, Rodrigues RJ et al (2006) Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1–A2A receptor heteromers. J Neurosci 26:.  https://doi.org/10.1523/JNEUROSCI.3574-05.2006
  10. 10.
    Machado-Filho JA, Correia AO, Montenegro ABA et al (2014) Caffeine neuroprotective effects on 6-OHDA-lesioned rats are mediated by several factors, including pro-inflammatory cytokines and histone deacetylase inhibitions. Behav Brain Res 264:116–125.  https://doi.org/10.1016/j.bbr.2014.01.051 CrossRefGoogle Scholar
  11. 11.
    Augusto E, Matos M, Sevigny J et al (2013) Ecto-5′-nucleotidase (CD73)-mediated formation of adenosine is critical for the striatal adenosine A2A receptor functions. J Neurosci 33:11390–11399.  https://doi.org/10.1523/JNEUROSCI.5817-12.2013 CrossRefGoogle Scholar
  12. 12.
    Eskelinen MH, Ngandu T, Tuomilehto J et al (2009) Midlife coffee and tea drinking and the risk of late-life dementia: A population-based CAIDE study. J Alzheimer’s Dis 16:85–91.  https://doi.org/10.3233/JAD-2009-0920 CrossRefGoogle Scholar
  13. 13.
    Kumar PM, Paing SST, Li H et al (2015) Differential effect of caffeine intake in subjects with genetic susceptibility to Parkinson’s disease. Sci Rep 5:15492.  https://doi.org/10.1038/srep15492 CrossRefGoogle Scholar
  14. 14.
    Costa MS, Botton PH, Mioranzza S et al (2008) Caffeine prevents age-associated recognition memory decline and changes brain-derived neurotrophic factor and tirosine kinase receptor (TrkB) content in mice. Neuroscience 153:1071–1078.  https://doi.org/10.1016/j.neuroscience.2008.03.038 CrossRefGoogle Scholar
  15. 15.
    Prediger RDS, Batista LC, Takahashi RN (2005) Caffeine reverses age-related deficits in olfactory discrimination and social recognition memory in rats: Involvement of adenosine A1 and A2A receptors. Neurobiol Aging 26:957–964.  https://doi.org/10.1016/j.neurobiolaging.2004.08.012 CrossRefGoogle Scholar
  16. 16.
    da Silva RS, Bruno AN, Battastini AMO et al (2003) Acute caffeine treatment increases extracellular nucleotide hydrolysis from rat striatal and hippocampal synaptosomes. Neurochem Res 28:1249–1254CrossRefGoogle Scholar
  17. 17.
    Quarta D, Ferré S, Solinas M et al (2004) Opposite modulatory roles for adenosine A1 and A2A receptors on glutamate and dopamine release in the shell of the nucleus accumbens. Effects of chronic caffeine exposure. J Neurochem 88:1151–1158.  https://doi.org/10.1046/j.1471-4159.2003.02245.x CrossRefGoogle Scholar
  18. 18.
    Chan K-M, Delfert D, Junger KD (1986) A direct colorimetric assay for Ca2+-stimulated ATPase activity. Anal Biochem 157:375–380.  https://doi.org/10.1016/0003-2697(86)90640-8 CrossRefGoogle Scholar
  19. 19.
    Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254.  https://doi.org/10.1016/0003-2697(76)90527-3 CrossRefGoogle Scholar
  20. 20.
    Liu Y, Peterson DA, Kimura H, Schubert D (1997) Mechanism of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. J Neurochem 69:581–593.  https://doi.org/10.1046/j.1471-4159.1997.69020581.x CrossRefGoogle Scholar
  21. 21.
    Leal RB, Cordova FM, Herd L et al (2002) Lead-stimulated p38MAPK-dependent Hsp27 phosphorylation. Toxicol Appl Pharmacol 178:44–51.  https://doi.org/10.1006/taap.2001.9320 CrossRefGoogle Scholar
  22. 22.
    Peterson GL (1977) A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem 83:346–356.  https://doi.org/10.1016/0003-2697(77)90043-4 CrossRefGoogle Scholar
  23. 23.
    Matos A, Ropelle ER, Pauli JR et al (2010) Acute exercise reverses TRB3 expression in the skeletal muscle and ameliorates whole body insulin sensitivity in diabetic mice. Acta Physiol 198:61–69.  https://doi.org/10.1111/j.1748-1716.2009.02031.x CrossRefGoogle Scholar
  24. 24.
    Peterson GL (1977) A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem 83:346–356CrossRefGoogle Scholar
  25. 25.
    Dhull DK, Bhateja D, Dhull RK, Padi SSV (2012) Differential role of cyclooxygenase isozymes on neuronal density in hippocampus CA1 region of intracerebroventricular streptozotocin treated rat brain. J Chem Neuroanat 43:48–51.  https://doi.org/10.1016/j.jchemneu.2011.10.001 CrossRefGoogle Scholar
  26. 26.
    Costenla AR, Cunha RA, De Mendonça A (2010) Caffeine, adenosine receptors, and synaptic plasticity. J Alzheimer’s Dis 20:.  https://doi.org/10.3233/JAD-2010-091384
  27. 27.
    Begg DP, Sinclair AJ, Weisinger RS (2012) Reductions in water and sodium intake by aged male and female rats. Nutr Res 32:865–872.  https://doi.org/10.1016/j.nutres.2012.09.014 CrossRefGoogle Scholar
  28. 28.
    Fredholm BB, Dunwiddie TV, Bergman B, Lindström K (1984) Levels of adenosine and adenine nucleotides in slices of rat hippocampus. Brain Res 295:127–136.  https://doi.org/10.1016/0006-8993(84)90823-0 CrossRefGoogle Scholar
  29. 29.
    Cunha RA, Almeida T, Ribeiro JA (2001) Parallel modification of adenosine extracellular metabolism and modulatory action in the hippocampus of aged rats. J Neurochem 76:372–382.  https://doi.org/10.1046/j.1471-4159.2001.00095.x CrossRefGoogle Scholar
  30. 30.
    Abbracchio MP, Burnstock G, Boeynaems J-M et al (2006) International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Pharmacol Rev 58:281–341.  https://doi.org/10.1124/pr.58.3.3 CrossRefGoogle Scholar
  31. 31.
    Heine P, Braun N, Heilbronn A, Zimmermann H (1999) Functional characterization of rat ecto-ATPase and ecto-ATP diphosphohydrolase after heterologous expression in CHO cells. Eur J Biochem 262:102–107.  https://doi.org/10.1046/j.1432-1327.1999.00347.x CrossRefGoogle Scholar
  32. 32.
    Sévigny J, Sundberg C, Braun N et al (2002) Differential catalytic properties and vascular topography of murine nucleoside triphosphate diphosphohydrolase 1 (NTPDase1) and NTPDase2 have implications for thromboregulation. Blood 99:2801–2809.  https://doi.org/10.1182/blood.V99.8.2801 CrossRefGoogle Scholar
  33. 33.
    Lavoie EG, Kukulski F, Lévesque SA et al (2004) Cloning and characterization of mouse nucleoside triphosphate diphosphohydrolase-3. Biochem Pharmacol 67:1917–1926.  https://doi.org/10.1016/j.bcp.2004.02.012 CrossRefGoogle Scholar
  34. 34.
    Murillo-Rodriguez E, Blanco-Centurion C, Gerashchenko D et al (2004) The diurnal rhythm of adenosine levels in the basal forebrain of young and old rats. Neuroscience 123:361–370.  https://doi.org/10.1016/j.neuroscience.2003.09.015 CrossRefGoogle Scholar
  35. 35.
    Mackiewicz M, Nikonova EV, Zimmermann JE et al (2006) Age-related changes in adenosine metabolic enzymes in sleep/wake regulatory areas of the brain. Neurobiol Aging 27:351–360.  https://doi.org/10.1016/j.neurobiolaging.2005.01.015 CrossRefGoogle Scholar
  36. 36.
    Fuchs JL (1991) 5′-Nucleotidase activity increases in aging rat brain. Neurobiol Aging 12:523–530.  https://doi.org/10.1016/0197-4580(91)90083-V CrossRefGoogle Scholar
  37. 37.
    Costenla AR, Diógenes MJ, Canas PM et al (2011) Enhanced role of adenosine A 2A receptors in the modulation of LTP in the rat hippocampus upon ageing. Eur J Neurosci 34:12–21.  https://doi.org/10.1111/j.1460-9568.2011.07719.x CrossRefGoogle Scholar
  38. 38.
    Canas PM, Duarte JMN, Rodrigues RJ et al (2009) Modification upon aging of the density of presynaptic modulation systems in the hippocampus. Neurobiol Aging 30:1877–1884.  https://doi.org/10.1016/j.neurobiolaging.2008.01.003 CrossRefGoogle Scholar
  39. 39.
    Svenningsson P, Nomikos GG, Fredholm BB (1999) The stimulatory action and the development of tolerance to caffeine is associated with alterations in gene expression in specific brain regions. J Neurosci 19:4011–4022CrossRefGoogle Scholar
  40. 40.
    Ballesteros-Yáñez I, Castillo CA, Amo-Salas M et al (2012) Differential effect of caffeine consumption on diverse brain areas of pregnant rats. J Caffeine Res 2:90–98.  https://doi.org/10.1089/jcr.2012.0011 CrossRefGoogle Scholar
  41. 41.
    Pintor A, Quarta D, Pèzzola A et al (2001) SCH 58261 (an adenosine A(2A) receptor antagonist) reduces, only at low doses, K(+)-evoked glutamate release in the striatum. Eur J Pharmacol 421:177–180.  https://doi.org/10.1016/S0014-2999(01)01058-5 CrossRefGoogle Scholar
  42. 42.
    Greene JG, Greenamyre JT (1996) Bioenergetics and glutamate excitotoxicity. Prog Neurobiol 48:613–634CrossRefGoogle Scholar
  43. 43.
    Kondo T, Mizuno Y, Japanese Istradefylline Study Group (2015) A long-term study of istradefylline safety and efficacy in patients with Parkinson disease. Clin Neuropharmacol 38:41–46.  https://doi.org/10.1097/WNF.0000000000000073 CrossRefGoogle Scholar
  44. 44.
    Schwarzschild MA, Agnati L, Fuxe K et al (2006) Targeting adenosine A2A receptors in Parkinson’s disease. Trends Neurosci 29:647–654.  https://doi.org/10.1016/j.tins.2006.09.004 CrossRefGoogle Scholar
  45. 45.
    Nassar NN, Abdel-Rahman AA (2015) Brain stem adenosine receptors modulate centrally mediated hypotensive responses in conscious rats: a review. J Adv Res 6:331–340.  https://doi.org/10.1016/j.jare.2014.12.005 CrossRefGoogle Scholar
  46. 46.
    Mori A (2014) Mode of action of adenosine A2A receptor antagonists as symptomatic treatment for Parkinson’s disease. Int Rev Neurobiol 119:87–116CrossRefGoogle Scholar
  47. 47.
    Vuorimaa A, Rissanen E, Airas L (2017) In vivo PET imaging of adenosine 2A receptors in neuroinflammatory and neurodegenerative disease. Contrast Media Mol Imaging 2017:1–15.  https://doi.org/10.1155/2017/6975841 CrossRefGoogle Scholar
  48. 48.
    Drapeau E, Mayo W, Aurousseau C et al (2003) Spatial memory performances of aged rats in the water maze predict levels of hippocampal neurogenesis. Proc Natl Acad Sci USA 100:14385–14390.  https://doi.org/10.1073/pnas.2334169100 CrossRefGoogle Scholar
  49. 49.
    Vila-Luna S, Cabrera-Isidoro S, Vila-Luna L et al (2012) Chronic caffeine consumption prevents cognitive decline from young to middle age in rats, and is associated with increased length, branching, and spine density of basal dendrites in CA1 hippocampal neurons. Neuroscience 202:384–395.  https://doi.org/10.1016/j.neuroscience.2011.11.053 CrossRefGoogle Scholar
  50. 50.
    Solfrizzi V, Panza F, Imbimbo BP et al (2015) Coffee consumption habits and the risk of mild cognitive impairment: the Italian longitudinal study on aging. J Alzheimer’s Dis 47:889–899.  https://doi.org/10.3233/JAD-150333 CrossRefGoogle Scholar
  51. 51.
    Damiani AP, Garcez ML, Letieli de Abreu L et al (2017) A reduction in DNA damage in neural tissue and peripheral blood of old mice treated with caffeine. J Toxicol Environ Heal Part A.  https://doi.org/10.1080/15287394.2017.1286901 Google Scholar
  52. 52.
    Ritchie K, Ancelin ML, Amieva H et al (2014) The association between caffeine and cognitive decline: examining alternative causal hypotheses. Int Psychogeriatr 26:581–590.  https://doi.org/10.1017/S1041610213002469 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Michelle Lima Garcez
    • 1
  • Adriani Paganini Damiani
    • 1
  • Robson Pacheco
    • 1
  • Lucas Rodrigues
    • 1
  • Larissa Letieli de Abreu
    • 1
  • Márcio Correa Alves
    • 1
  • Vanessa Moraes de Andrade
    • 1
  • Carina Rodrigues Boeck
    • 2
  1. 1.Laboratório de Biologia Celular e Molecular, Programa de Pós-Graduação em Ciências da SaúdeUniversidade do Extremo Sul Catarinense – UNESCCriciúmaBrazil
  2. 2.Programa de Pós-graduação em NanociênciasCentro Universitário Franciscano -UNIFRASanta MariaBrazil

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