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Early synaptic deficits in the APP/PS1 mouse model of Alzheimer’s disease involve neuronal adenosine A2A receptors

Author

Listed:
  • Silvia Viana da Silva

    (Interdisciplinary Institute for Neuroscience, University of Bordeaux
    BEB PhD program CNC Coimbra)

  • Matthias Georg Haberl

    (University of Bordeaux, Neurocentre Magendie, INSERM U862, F-33000 Bordeaux, France)

  • Pei Zhang

    (Interdisciplinary Institute for Neuroscience, University of Bordeaux)

  • Philipp Bethge

    (Interdisciplinary Institute for Neuroscience, University of Bordeaux)

  • Cristina Lemos

    (CNC-Center for Neuroscience and Cell Biology, University of Coimbra)

  • Nélio Gonçalves

    (CNC-Center for Neuroscience and Cell Biology, University of Coimbra)

  • Adam Gorlewicz

    (Interdisciplinary Institute for Neuroscience, University of Bordeaux)

  • Meryl Malezieux

    (Interdisciplinary Institute for Neuroscience, University of Bordeaux)

  • Francisco Q. Gonçalves

    (CNC-Center for Neuroscience and Cell Biology, University of Coimbra)

  • Noëlle Grosjean

    (Interdisciplinary Institute for Neuroscience, University of Bordeaux)

  • Christophe Blanchet

    (Interdisciplinary Institute for Neuroscience, University of Bordeaux)

  • Andreas Frick

    (University of Bordeaux, Neurocentre Magendie, INSERM U862, F-33000 Bordeaux, France)

  • U Valentin Nägerl

    (Interdisciplinary Institute for Neuroscience, University of Bordeaux)

  • Rodrigo A. Cunha

    (CNC-Center for Neuroscience and Cell Biology, University of Coimbra
    Faculty of Medicine, University of Coimbra)

  • Christophe Mulle

    (Interdisciplinary Institute for Neuroscience, University of Bordeaux)

Abstract

Synaptic plasticity in the autoassociative network of recurrent connections among hippocampal CA3 pyramidal cells is thought to enable the storage of episodic memory. Impaired episodic memory is an early manifestation of cognitive deficits in Alzheimer’s disease (AD). In the APP/PS1 mouse model of AD amyloidosis, we show that associative long-term synaptic potentiation (LTP) is abolished in CA3 pyramidal cells at an early stage. This is caused by activation of upregulated neuronal adenosine A2A receptors (A2AR) rather than by dysregulation of NMDAR signalling or altered dendritic spine morphology. Neutralization of A2AR by acute pharmacological inhibition, or downregulation driven by shRNA interference in a single postsynaptic neuron restore associative CA3 LTP. Accordingly, treatment with A2AR antagonists reverts one-trial memory deficits. These results provide mechanistic support to encourage testing the therapeutic efficacy of A2AR antagonists in early AD patients.

Suggested Citation

  • Silvia Viana da Silva & Matthias Georg Haberl & Pei Zhang & Philipp Bethge & Cristina Lemos & Nélio Gonçalves & Adam Gorlewicz & Meryl Malezieux & Francisco Q. Gonçalves & Noëlle Grosjean & Christophe, 2016. "Early synaptic deficits in the APP/PS1 mouse model of Alzheimer’s disease involve neuronal adenosine A2A receptors," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11915
    DOI: 10.1038/ncomms11915
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    Cited by:

    1. Muran Wang & Peijun Li & Zewen Li & Beatriz S. Silva & Wu Zheng & Zhenghua Xiang & Yan He & Tao Xu & Cristina Cordeiro & Lu Deng & Yuwei Dai & Mengqian Ye & Zhiqing Lin & Jianhong Zhou & Xuzhao Zhou &, 2023. "Lateral septum adenosine A2A receptors control stress-induced depressive-like behaviors via signaling to the hypothalamus and habenula," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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