Caffeine Neuroprotection Decreases A2A Adenosine Receptor Content in Aged Mice
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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.
KeywordsAging Adenosine receptors Caffeine Ecto-NTPDase Ecto-5′-nucleotidase
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).
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
The authors declare that there is no conflict of interests regarding the publication of this paper.
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).
- 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
- 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.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
- 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.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
- 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
- 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
- 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
- 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
- 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.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
- 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
- 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