Neurochemical Research

, Volume 44, Issue 4, pp 787–795 | Cite as

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 BoeckEmail author
Original Paper


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.


Aging 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).

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


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).


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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
    Email author
  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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