Platelet factors attenuate inflammation and rescue cognition in ageing.

Autor: Schroer AB; Department of Anatomy, University of California San Francisco, San Francisco, CA, USA. adam.schroer@ucsf.edu., Ventura PB; Department of Anatomy, University of California San Francisco, San Francisco, CA, USA., Sucharov J; Department of Anatomy, University of California San Francisco, San Francisco, CA, USA.; Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA, USA., Misra R; Department of Anatomy, University of California San Francisco, San Francisco, CA, USA.; Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA, USA., Chui MKK; Department of Anatomy, University of California San Francisco, San Francisco, CA, USA., Bieri G; Department of Anatomy, University of California San Francisco, San Francisco, CA, USA., Horowitz AM; Department of Anatomy, University of California San Francisco, San Francisco, CA, USA.; Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA, USA., Smith LK; Department of Anatomy, University of California San Francisco, San Francisco, CA, USA.; Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA, USA., Encabo K; Department of Urology, University of California San Francisco, San Francisco, CA, USA., Tenggara I; Department of Urology, University of California San Francisco, San Francisco, CA, USA., Couthouis J; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA., Gross JD; Department of Cell Biology, Duke University, Durham, NC, USA., Chan JM; Department of Urology, University of California San Francisco, San Francisco, CA, USA.; Departments of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA., Luke A; Department of Orthopaedics, University of California San Francisco, San Francisco, CA, USA., Villeda SA; Department of Anatomy, University of California San Francisco, San Francisco, CA, USA. saul.villeda@ucsf.edu.; Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA, USA. saul.villeda@ucsf.edu.; Department of Physical Therapy and Rehabilitation Science, University of California San Francisco, San Francisco, CA, USA. saul.villeda@ucsf.edu.; Bakar Aging Research Institute, University of California San Francisco, San Francisco, CA, USA. saul.villeda@ucsf.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2023 Aug; Vol. 620 (7976), pp. 1071-1079. Date of Electronic Publication: 2023 Aug 16.
DOI: 10.1038/s41586-023-06436-3
Abstrakt: Identifying therapeutics to delay, and potentially reverse, age-related cognitive decline is critical in light of the increased incidence of dementia-related disorders forecasted in the growing older population 1 . Here we show that platelet factors transfer the benefits of young blood to the ageing brain. Systemic exposure of aged male mice to a fraction of blood plasma from young mice containing platelets decreased neuroinflammation in the hippocampus at the transcriptional and cellular level and ameliorated hippocampal-dependent cognitive impairments. Circulating levels of the platelet-derived chemokine platelet factor 4 (PF4) (also known as CXCL4) were elevated in blood plasma preparations of young mice and humans relative to older individuals. Systemic administration of exogenous PF4 attenuated age-related hippocampal neuroinflammation, elicited synaptic-plasticity-related molecular changes and improved cognition in aged mice. We implicate decreased levels of circulating pro-ageing immune factors and restoration of the ageing peripheral immune system in the beneficial effects of systemic PF4 on the aged brain. Mechanistically, we identified CXCR3 as a chemokine receptor that, in part, mediates the cellular, molecular and cognitive benefits of systemic PF4 on the aged brain. Together, our data identify platelet-derived factors as potential therapeutic targets to abate inflammation and rescue cognition in old age.
(© 2023. The Author(s).)
Databáze: MEDLINE
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