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other·neurology, preclinical research, biomedical research, geriatrics·PMC10432533

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

Nature Communications · 13 authors, 6 centres

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TL;DR

This preclinical study in aged mice shows that exercise activates platelets, which secrete the exerkine CXCL4/platelet factor 4 (PF4). Administration of PF4 was sufficient to increase hippocampal neurogenesis and improve cognitive function in a manner dependent on neurogenesis.

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The study investigated how exercise benefits the aging brain, focusing on platelets as a source of circulating factors. Using aged mice, researchers found that exercise activates platelets, which are required for exercise-induced hippocampal precursor cell proliferation. Systemic administration of the platelet-derived chemokine CXCL4/platelet factor 4 (PF4) was shown to increase hippocampal neurogenesis, improve neuronal dendrite morphology, and restore cognitive function in aged mice. These effects were dependent on hippocampal neurogenesis. The research identifies PF4 as an exercise-mimetic that can rejuvenate regenerative and cognitive impairments associated with aging. Limitations include the use of a mouse model, and the precise cellular mechanisms by which PF4 acts on the neural stem cell niche remain to be determined. The findings suggest a potential therapeutic avenue for age-related cognitive decline.

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other

SPECIALTY

neurology

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AI pipeline

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100% · A

ORIGINAL PAPER

PMC10432533

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

Nature Communications

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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.

CITATION EXPORT

Odette Leiter, David Brici, Stephen J. Fletcher et al.. Platelet-derived exerkine CXCL4/platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice. Nature Communications. (2023). https://doi.org/10.1038/s41467-023-39873-9

AUTHORS

13 · 6 CENTRES

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 Anggono, Saul A. Villeda, Tara L. Walker

1https://ror.org/00rqy9422grid.1003.20000 0000 9320 7537Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072 Australia
2https://ror.org/00rqy9422grid.1003.20000 0000 9320 7537Centre for Horticultural Science, Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, Brisbane, QLD 4072 Australia
3grid.1003.20000 0000 9320 7537Queensland Cyber Infrastructure Foundation Ltd, The University of Queensland, Brisbane, QLD 4072 Australia
4https://ror.org/043mz5j54grid.266102.10000 0001 2297 6811Department of Anatomy, University of California San Francisco, San Francisco, CA 94143 USA
5https://ror.org/043mz5j54grid.266102.10000 0001 2297 6811The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143 USA
6grid.266102.10000 0001 2297 6811Bakar Aging Research Institute, University of California San Francisco, San Francisco, CA 94143 USA