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Rescue of astrocyte activity by the calcium sensor STIM1 restores long-term synaptic plasticity in female mice modelling Alzheimer’s disease

Author

Listed:
  • Annamaria Lia

    (National Research Council (CNR)
    University of Padua)

  • Gabriele Sansevero

    (National Research Council (CNR)
    University of Florence)

  • Angela Chiavegato

    (University of Padua)

  • Miriana Sbrissa

    (University of Padua)

  • Diana Pendin

    (National Research Council (CNR)
    University of Padua)

  • Letizia Mariotti

    (National Research Council (CNR)
    University of Padua)

  • Tullio Pozzan

    (National Research Council (CNR)
    University of Padua
    Foundation for Advanced Biomedical Research)

  • Nicoletta Berardi

    (National Research Council (CNR)
    University of Florence)

  • Giorgio Carmignoto

    (National Research Council (CNR)
    University of Padua)

  • Cristina Fasolato

    (University of Padua)

  • Micaela Zonta

    (National Research Council (CNR)
    University of Padua)

Abstract

Calcium dynamics in astrocytes represent a fundamental signal that through gliotransmitter release regulates synaptic plasticity and behaviour. Here we present a longitudinal study in the PS2APP mouse model of Alzheimer’s disease (AD) linking astrocyte Ca2+ hypoactivity to memory loss. At the onset of plaque deposition, somatosensory cortical astrocytes of AD female mice exhibit a drastic reduction of Ca2+ signaling, closely associated with decreased endoplasmic reticulum Ca2+ concentration and reduced expression of the Ca2+ sensor STIM1. In parallel, astrocyte-dependent long-term synaptic plasticity declines in the somatosensory circuitry, anticipating specific tactile memory loss. Notably, we show that both astrocyte Ca2+ signaling and long-term synaptic plasticity are fully recovered by selective STIM1 overexpression in astrocytes. Our data unveil astrocyte Ca2+ hypoactivity in neocortical astrocytes as a functional hallmark of early AD stages and indicate astrocytic STIM1 as a target to rescue memory deficits.

Suggested Citation

  • Annamaria Lia & Gabriele Sansevero & Angela Chiavegato & Miriana Sbrissa & Diana Pendin & Letizia Mariotti & Tullio Pozzan & Nicoletta Berardi & Giorgio Carmignoto & Cristina Fasolato & Micaela Zonta, 2023. "Rescue of astrocyte activity by the calcium sensor STIM1 restores long-term synaptic plasticity in female mice modelling Alzheimer’s disease," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37240-2
    DOI: 10.1038/s41467-023-37240-2
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    References listed on IDEAS

    as
    1. Andrea Delekate & Martina Füchtemeier & Toni Schumacher & Cordula Ulbrich & Marco Foddis & Gabor C. Petzold, 2014. "Metabotropic P2Y1 receptor signalling mediates astrocytic hyperactivity in vivo in an Alzheimer’s disease mouse model," Nature Communications, Nature, vol. 5(1), pages 1-14, December.
    2. Hiromu Monai & Masamichi Ohkura & Mika Tanaka & Yuki Oe & Ayumu Konno & Hirokazu Hirai & Katsuhiko Mikoshiba & Shigeyoshi Itohara & Junichi Nakai & Youichi Iwai & Hajime Hirase, 2016. "Calcium imaging reveals glial involvement in transcranial direct current stimulation-induced plasticity in mouse brain," Nature Communications, Nature, vol. 7(1), pages 1-10, September.
    3. Letizia Mariotti & Gabriele Losi & Annamaria Lia & Marcello Melone & Angela Chiavegato & Marta Gómez-Gonzalo & Michele Sessolo & Serena Bovetti & Angelo Forli & Micaela Zonta & Linda Maria Requie & Ia, 2018. "Interneuron-specific signaling evokes distinctive somatostatin-mediated responses in adult cortical astrocytes," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
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