神经炎症
老化
认知功能衰退
炎症
医学
痴呆
海马结构
全身炎症
免疫学
趋化因子
免疫系统
血小板
小胶质细胞
认知
免疫失调
海马体
血小板因子4
神经科学
内科学
心理学
疾病
作者
Adam B. Schroer,Patrick Ventura,Juliana Sucharov,Rhea Misra,M K Kirsten Chui,Gregor Bieri,Alana Horowitz,Lucas K. Smith,Katriel Encabo,Imelda Tenggara,Julien Couthouis,Joshua Gross,June M. Chan,Anthony Luke,Saul Villeda
出处
期刊:Nature
[Nature Portfolio]
日期:2023-08-16
卷期号:620 (7976): 1071-1079
被引量:119
标识
DOI:10.1038/s41586-023-06436-3
摘要
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 population1. 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.
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