Platelet factors attenuate inflammation and rescue cognition in ageing.
Adam B SchroerPatrick B VenturaJuliana SucharovRhea MisraM K Kirsten ChuiGregor BieriAlana M HorowitzLucas K SmithKatriel EncaboImelda TenggaraJulien CouthouisJoshua D GrossJune M ChanAnthony LukeSaul A VilledaPublished in: Nature (2023)
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.
Keyphrases
- mild cognitive impairment
- cerebral ischemia
- cognitive decline
- white matter
- middle aged
- cognitive impairment
- oxidative stress
- high fat diet induced
- resting state
- traumatic brain injury
- physical activity
- blood brain barrier
- brain injury
- risk factors
- small molecule
- single molecule
- risk assessment
- adipose tissue
- type diabetes
- machine learning
- community dwelling
- skeletal muscle
- climate change
- artificial intelligence
- red blood cell
- chemotherapy induced