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Platelet-derived exerkine CXCL4/platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice

Author

Listed:
  • Odette Leiter

    (The University of Queensland)

  • David Brici

    (The University of Queensland)

  • Stephen J. Fletcher

    (The University of Queensland)

  • Xuan Ling Hilary Yong

    (The University of Queensland)

  • Jocelyn Widagdo

    (The University of Queensland)

  • Nicholas Matigian

    (The University of Queensland)

  • Adam B. Schroer

    (University of California San Francisco)

  • Gregor Bieri

    (University of California San Francisco)

  • Daniel G. Blackmore

    (The University of Queensland)

  • Perry F. Bartlett

    (The University of Queensland)

  • Victor Anggono

    (The University of Queensland)

  • Saul A. Villeda

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

  • Tara L. Walker

    (The University of Queensland)

Abstract

The beneficial effects of physical activity on brain ageing are well recognised, with exerkines, factors that are secreted into the circulation in response to exercise, emerging as likely mediators of this response. However, the source and identity of these exerkines remain unclear. Here we provide evidence that an anti-geronic exerkine is secreted by platelets. We show that platelets are activated by exercise and are required for the exercise-induced increase in hippocampal precursor cell proliferation in aged mice. We also demonstrate that increasing the systemic levels of the platelet-derived exerkine CXCL4/platelet factor 4 (PF4) ameliorates age-related regenerative and cognitive impairments in a hippocampal neurogenesis-dependent manner. Together these findings highlight the role of platelets in mediating the rejuvenating effects of exercise during physiological brain ageing.

Suggested Citation

  • Odette Leiter & David Brici & Stephen J. Fletcher & Xuan Ling Hilary Yong & Jocelyn Widagdo & Nicholas Matigian & Adam B. Schroer & Gregor Bieri & Daniel G. Blackmore & Perry F. Bartlett & Victor Angg, 2023. "Platelet-derived exerkine CXCL4/platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39873-9
    DOI: 10.1038/s41467-023-39873-9
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    1. Zurine Miguel & Nathalie Khoury & Michael J. Betley & Benoit Lehallier & Drew Willoughby & Niclas Olsson & Andrew C. Yang & Oliver Hahn & Nannan Lu & Ryan T. Vest & Liana N. Bonanno & Lakshmi Yerra & , 2021. "Exercise plasma boosts memory and dampens brain inflammation via clusterin," Nature, Nature, vol. 600(7889), pages 494-499, December.
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