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Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice

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Listed:
  • Kanchan Bisht

    (University of Virginia School of Medicine
    University of Virginia)

  • Kenneth A. Okojie

    (University of Virginia School of Medicine
    University of Virginia)

  • Kaushik Sharma

    (University of Virginia School of Medicine
    University of Virginia)

  • Dennis H. Lentferink

    (University of Virginia School of Medicine
    University of Virginia)

  • Yu-Yo Sun

    (University of Virginia School of Medicine
    University of Virginia)

  • Hong-Ru Chen

    (University of Virginia School of Medicine
    University of Virginia)

  • Joseph O. Uweru

    (University of Virginia School of Medicine
    University of Virginia)

  • Saipranusha Amancherla

    (University of Virginia School of Medicine)

  • Zainab Calcuttawala

    (University of Virginia School of Medicine)

  • Antony Brayan Campos-Salazar

    (University of Virginia School of Medicine
    University of Virginia)

  • Bruce Corliss

    (University of Virginia School of Medicine)

  • Lara Jabbour

    (University of Virginia School of Medicine)

  • Jordan Benderoth

    (University of Virginia School of Medicine)

  • Bria Friestad

    (University of Virginia School of Medicine
    University of Virginia)

  • William A. Mills

    (University of Virginia School of Medicine
    University of Virginia
    University of Virginia School of Medicine)

  • Brant E. Isakson

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Marie-Ève Tremblay

    (Centre de recherche du CHU de Québec—Université Laval
    Université Laval
    McGill University
    University of Victoria)

  • Chia-Yi Kuan

    (University of Virginia School of Medicine
    University of Virginia)

  • Ukpong B. Eyo

    (University of Virginia School of Medicine
    University of Virginia
    University of Virginia School of Medicine)

Abstract

Microglia are brain-resident immune cells with a repertoire of functions in the brain. However, the extent of their interactions with the vasculature and potential regulation of vascular physiology has been insufficiently explored. Here, we document interactions between ramified CX3CR1 + myeloid cell somata and brain capillaries. We confirm that these cells are bona fide microglia by molecular, morphological and ultrastructural approaches. Then, we give a detailed spatio-temporal characterization of these capillary-associated microglia (CAMs) comparing them with parenchymal microglia (PCMs) in their morphological activities including during microglial depletion and repopulation. Molecularly, we identify P2RY12 receptors as a regulator of CAM interactions under the control of released purines from pannexin 1 (PANX1) channels. Furthermore, microglial elimination triggered capillary dilation, blood flow increase, and impaired vasodilation that were recapitulated in P2RY12−/− and PANX1−/− mice suggesting purines released through PANX1 channels play important roles in activating microglial P2RY12 receptors to regulate neurovascular structure and function.

Suggested Citation

  • Kanchan Bisht & Kenneth A. Okojie & Kaushik Sharma & Dennis H. Lentferink & Yu-Yo Sun & Hong-Ru Chen & Joseph O. Uweru & Saipranusha Amancherla & Zainab Calcuttawala & Antony Brayan Campos-Salazar & B, 2021. "Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25590-8
    DOI: 10.1038/s41467-021-25590-8
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    Cited by:

    1. Janos Groh & Tassnim Abdelwahab & Yogita Kattimani & Michaela Hörner & Silke Loserth & Viktoria Gudi & Robert Adalbert & Fabian Imdahl & Antoine-Emmanuel Saliba & Michael Coleman & Martin Stangel & Mi, 2023. "Microglia-mediated demyelination protects against CD8+ T cell-driven axon degeneration in mice carrying PLP defects," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    2. George Sideris-Lampretsas & Silvia Oggero & Lynda Zeboudj & Rita Silva & Archana Bajpai & Gopuraja Dharmalingam & David A. Collier & Marzia Malcangio, 2023. "Galectin-3 activates spinal microglia to induce inflammatory nociception in wild type but not in mice modelling Alzheimer’s disease," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Sally H. Mohamed & Man Shun Fu & Sofia Hain & Alanoud Alselami & Eliane Vanhoffelen & Yanjian Li & Ebrima Bojang & Robert Lukande & Elizabeth R. Ballou & Robin C. May & Chen Ding & Greetje Vande Velde, 2023. "Microglia are not protective against cryptococcal meningitis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Fan Li & Jazlyn Gallego & Natasha N. Tirko & Jenna Greaser & Derek Bashe & Rudra Patel & Eric Shaker & Grace E. Valkenburg & Alanoud S. Alsubhi & Steven Wellman & Vanshika Singh & Camila Garcia Padill, 2024. "Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    5. William A. Mills & AnnaLin M. Woo & Shan Jiang & Joelle Martin & Dayana Surendran & Matthew Bergstresser & Ian F. Kimbrough & Ukpong B. Eyo & Michael V. Sofroniew & Harald Sontheimer, 2022. "Astrocyte plasticity in mice ensures continued endfoot coverage of cerebral blood vessels following injury and declines with age," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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