Could injections of young cerebrospinal fluid rejuvenate older brains and delay cognitive decline?

Scientists have reversed memory loss in older mice by injecting them with a brain fluid from younger peers in a “groundbreaking” new treatment. The substance — called cerebrospinal fluid (CSF) — washes in and out of gray and white brain matter in waves, helping clear out waste.

It bathes the tissue with proteins, or growth factors, that are vital for normal development. However, CSF levels drop off as we get older, increasing the risk of Alzheimer’s and other neurological conditions. The therapy opens the door to new treatments which could slow cognitive decline, according to scientists at Stanford University.

Using a tiny tube and pump, the team infused CSF from young adult mice into the brains of 18-month-old animals for seven days. In “mice years,” this is the equivalent being a 60-year-old person.

Scans showed the transfusion boosted production of myelin, a fatty sheath that protects neurons from damage. Afterwards, the elderly mice got better at a “fear conditioning” task. They remembered a tone and flashing light signaling that the mice were about to receive a small electric shock.

“Brain aging underlies dementia and neurodegenerative diseases, imposing an immense societal burden,” corresponding author Professor Tony Wyss-Coray of Stanford says in a statement per South West News Service. “Memory improvements that are seen in old mice receiving CSF from younger animals may be attributed to growth factors that are shown to restore neural cell function. The findings demonstrate the potential rejuvenating properties of young CSF for the aging brain.”

Altering the memory center of the brain

Study authors used RNA sequencing to show that the therapy altered gene expression in the hippocampus, the brain region which controls memory. It stimulated cells in the central nervous system known as oligodendrocytes. They make myelin, ensuring strong signals between neurons.

The study in the journal Nature reports that genes that are typically expressed in oligodendrocytes were highly upregulated in old mice treated with CSF from young mice. In particular, it identified a gene named Fgf17 as being key. Activity decreases in aged mice.

Boosting the gene achieved the same benefits as young CSF, offering hope of developing a drug that targets it.

“As the brain ages, cognitive decline increases along with the risk of dementia and neurodegenerative disease,” Prof. Wyss-Coray explains. “An understanding of how systemic factors affect the brain throughout life has shed light on potential treatments to slow brain aging. The CSF is part of the immediate environment of the brain, providing brain cells with nutrients, signaling molecules and growth factors.”

Age-related cognitive decline affects up to one in four adults over 60 years-old. A healthy diet and regular exercise protects against it, but there are no pharmacological treatments currently.

“These findings demonstrate the rejuvenating power of young CSF and identify Fgf17 as a key target to restore oligodendrocyte function in the aging brain,” study authors write.

“Combined, our results suggest that targeting hippocampal myelination through factors present in young CSF might be a therapeutic strategy to prevent or rescue cognitive decline associated with aging and neurodegenerative diseases.”

‘Groundbreaking’ treatment for dementia

Dr. Miriam Zawadzki and Prof. Maria Lehtinen, of Boston Children’s Hospital in Massachusetts who did not take part in the study, described the work as “groundbreaking.”

“Not only does the study imply FGF17 has potential as a therapeutic target, but it also suggests routes of drug administration that allow therapeutics to directly access the CSF could be beneficial in treating dementia,” they say in a statement provided by SWNS. “Any such treatments will be hugely helpful in supporting our ageing population.”

The number of dementia cases across the world are set to triple to more than 150 million by 2050. In the U.S., Alzheimer’s and other forms of the disease affect over six million people.

South West News Service writer Mark Waghorn contributed to this report.

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