Researchers find they can reverse memory loss in mice by transferring cerebrospinal fluid from young to older rodents.
Cerebrospinal fluid (CSF) is a clear fluid found in the tissue surrounding the brain and the spinal cord of all living vertebrates. It flows in and out of grey and white matter, helping to eliminate waste. It also cleanses protein tissue which is crucial for normal development. Now, researchers have found that cognitive decline can be reversed in mice by injecting them with CSF from younger rodents. Their study, published in the journal Nature, presents this new treatment as a way of potentially reversing memory loss in humans.
The amount of CSF produced by the body lessens with age, often leading to the onset of cognitive decline, Alzheimer’s disease and other neurological disorders. “The therapy opens the door to new treatments and the slowing cognitive decline,” scientists wrote.
Over the course of a week, the team use a tube and pump to transfer CSF from young adult mice into the brains of 18-month-old mice (which they say is equivalent to about 60 years of age in human). Subsequent brain scans showed the transfer of CSF increased the production of myelin, which protects neurons from damage. RNA sequencing showed the transfer also altered gene expression in the hippocampus, which is responsible for controlling memory.
“Afterwards, the elderly mice got better at a ‘fear-conditioning task,’” the team wrote. “They remembered a tone and flashing light meant they were about to receive a small electric shock.”
Author Professor Tony Wyss-Coray of Stanford University in California said, “Brain aging underlies dementia and neurodegenerative diseases, imposing an immense societal burden. 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.”
The study also found genes expressed in oligodendrocytes were “highly up regulated in old mice treated with CSF from young mice. In particular, boosting a gene known as Fgf17 “achieved the same benefits as young CSF.”
Wyss-Coray explained, “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 aging. The CSF is part of the immediate environment of the brain, providing brain cells with nutrients, signaling molecules and growth factors.”
There are currently no known pharmaceutical treatments that slow the progression of cognitive decline, although some lifestyle changes (such as maintaining a regular exercise routine) can help.
“These findings demonstrate the rejuvenating power of young CSF and identify Fgf17 as a key target to restore oligodendrocyte function in the aging brain,” Prof Wyss-Coray said. “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 ageing and neurodegenerative diseases.”
Dr. Miriam Zawadzki and Professor Maria Lehtinen, of Boston Children’s Hospital, responded to the findings, “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. Any such treatments will be hugely helpful in supporting our aging population.”
Sources:
Memory Loss Was Reversed in Mice Using a Brain Liquid from Younger Peers in ‘Groundbreaking’ Study
Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17
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