Ageing: Cerebrospinal fluid from young mice improves memory in old mice

Memory improvements that are seen in old mice receiving cerebrospinal fluid (CSF) from younger animals may be attributed to growth factors that are shown to restore neural cell function, a study published in Nature reports. The findings demonstrate the potential rejuvenating properties of young CSF for the ageing brain.

As the brain ages, cognitive decline increases along with the risk of dementia and neurodegenerative disease. An understanding of how systemic factors affect the brain throughout life has shed light on potential treatments to slow brain ageing. The CSF is part of the immediate environment of the brain, providing brain cells with nutrients, signalling molecules and growth factors, but its role in brain ageing is not well understood.

To test the potential rejuvenating properties of CSF, Tony Wyss-Coray and colleagues infuse CSF from young mice (10 weeks old) into the brains of older mice (18 months old). The treatment improves memory function of old animals, the authors report. Young CSF is shown to increase the stimulation of cells called oligodendrocyte precursor cells — which have the potential to regenerate oligodendrocytes (a type of neural cell) and myelin (a fatty material that protects nerve cells) — within the hippocampus, the memory centre of the brain.

To determine the mechanisms underlying these effects, the authors look at the signalling pathways activated by young CSF. A transcription factor known as SRF is found to mediate the effects of young CSF on the oligodendrocyte precursor cells, and expression of this factor is shown to decrease in the hippocampus of older mice. The authors also identify a growth factor known as Fgf17 as a candidate for inducing SRF signalling. Expression of Fgf17 is shown to decrease in aged mice. However, infusion of the growth factor into old mice reproduces the effects seen with infusion of young CSF, inducing oligodendrocyte precursor cell proliferation and improving memory function.

These findings identify Fgf17 as a potential rejuvenating factor for the ageing brain, the authors conclude. “Not only does the study imply that FGF17 has potential as a therapeutic target, but it also suggests that routes of drug administration that allow therapeutics to directly access the CSF could be beneficial in treating dementia,” write Miriam Zawadzki and Maria Lehtinen in an accompanying News & Views.