PDF(Pubmed)
Abstract：
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.
摘要：
确定延迟治疗方法，并可能逆转，考虑到在越来越多的老年人群中预测的痴呆相关疾病的发病率增加,年龄相关的认知功能下降至关重要1.在这里，我们表明血小板因子将年轻血液的益处转移到衰老的大脑。老年雄性小鼠全身暴露于含有血小板的年轻小鼠的一部分血浆中，在转录和细胞水平上减少了海马中的神经炎症，并改善了海马依赖性认知障碍。血小板衍生的趋化因子血小板因子4（PF4）（也称为CXCL4）的循环水平在年轻小鼠和人类的血浆制剂中相对于老年个体升高。全身性给予外源性PF4减轻与年龄相关的海马神经炎症，在老年小鼠中引起突触可塑性相关的分子变化并改善认知。我们暗示，在全身PF4对老年大脑的有益作用中，循环前衰老免疫因子的水平降低和衰老的外周免疫系统的恢复。机械上,我们确定CXCR3是一种趋化因子受体，在某种程度上,介导细胞，全身PF4对老年大脑的分子和认知益处。一起,我们的数据将血小板衍生因子确定为老年患者减轻炎症和挽救认知的潜在治疗靶点.
