Can platelets mediate adult hippocampal neurogenesis and cognitive function in the aged brain?
Final Report Abstract
This project investigated the role of platelets in regulating new neuron generation in the adult hippocampus (adult neurogenesis) and their potential to mediate hippocampal learning and memory in the aged brain. Adult hippocampal neurogenesis continues throughout life, however, the rate at which the new brain cells are produced declines with age. This decline is associated with reduced learning and memory function and ways to boost adult neurogenesis represent a promising approach to slow or restore age-related cognitive impairments. This project identified platelets, small cells in our blood, and factors they release following exercise as important mediators of adult hippocampal neurogenesis in the aged hippocampus. The work shows that platelets become activated during exercise, which leads to changes in their proteomic signature and the release of neurogenesis-promoting platelet proteins into the blood. Platelet factor 4, one of the released exercise factors, was investigated in more detail, and identified as a pro-neurogenic protein, which upon systemic administration into the blood stream of aged mice, enhanced ongoing neurogenesis and cognitive capacity in the animals. The findings highlight an essential role of platelets and the factors they release in mediating brain function, and could lead to the development of therapeutic approaches to restore agerelated cognitive decline.
Publications
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Platelet-derived exerkine CXCL4/platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice. Nature Communications, 14(1).
Leiter, Odette; Brici, David; Fletcher, Stephen J.; Yong, Xuan Ling Hilary; Widagdo, Jocelyn; Matigian, Nicholas; Schroer, Adam B.; Bieri, Gregor; Blackmore, Daniel G.; Bartlett, Perry F.; Anggono, Victor; Villeda, Saul A. & Walker, Tara L.
