Enhanced role of adenosine A2A receptors in the modulation of LTP in the rat hippocampus upon ageing

Authors

  • Ana R. Costenla,

    1. Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
    2. Unit of Neuroscience, Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
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  • Maria J. Diógenes,

    1. Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
    2. Unit of Neuroscience, Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
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  • Paula M. Canas,

    1. Center for Neuroscience of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal
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  • Ricardo J. Rodrigues,

    1. Center for Neuroscience of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal
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  • Célia Nogueira,

    1. Institute of Microbiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
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  • João Maroco,

    1. Instituto Superior de Psicologia Aplicada, Lisbon, Portugal
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  • Paula M. Agostinho,

    1. Center for Neuroscience of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal
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  • Joaquim A. Ribeiro,

    1. Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
    2. Unit of Neuroscience, Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
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  • Rodrigo A. Cunha,

    1. Center for Neuroscience of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal
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  • Alexandre de Mendonça

    1. Unit of Neuroscience, Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
    2. Laboratory of Neurosciences and Department of Neurology, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
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Dr R. A. Cunha, as above.
E-mail: cunharod@gmail.com

Abstract

Adenosine neuromodulation depends on a balanced activation of inhibitory A1 (A1R) and facilitatory A2A receptors (A2AR). Both A1R and A2AR modulate hippocampal glutamate release and NMDA-dependent long-term potentiation (LTP) but ageing affects the density of both A1R and A2AR. We tested the effects of selective A1R and A2AR antagonists in the modulation of synaptic transmission and plasticity in rat hippocampal slices from three age groups (young adults, 2–3 month; middle-aged adults, 6–8 months; aged, 18–20 months). The selective A2AR antagonist SCH58261 (50 nm) attenuated LTP in all age groups, with a larger effect in aged (−63 ± 7%) than in middle-aged adults (−36 ± 9%) or young adult rats (−36 ± 9%). In contrast, the selective A1R antagonist DPCPX (50 nm) increased LTP magnitude in young adult rats (+42 ± 6%), but failed to affect LTP magnitude in the other age groups. Finally, in the continuous presence of DPCPX, SCH58261 caused a significantly larger inhibition of LTP amplitude in aged (−71 ± 45%) than middle-aged (−28 ± 9%) or young rats (−11 ± 2%). Accordingly, aged rats displayed an increased expression of A2AR mRNA in the hippocampus and a higher number of glutamatergic nerve terminals equipped with A2AR in aged (67 ± 6%) compared with middle-aged (34 ± 7%) and young rats (25 ± 5%). The results show an enhanced A2AR-mediated modulation of LTP in aged rats, in accordance with the age-associated increased expression and density of A2AR in glutamatergic terminals. This age-associated gain of function of A2AR modulating synaptic plasticity may underlie the ability of A2AR antagonists to prevent memory dysfunction in aged animals.

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