From Younger Animals to Older Animals: Cerebrospinal fluid exchange improves memory

From the youngest to the oldest animals
Cerebrospinal fluid exchange improves memory

Dementia, Parkinson’s, multiple sclerosis: untreatable neurodegenerative diseases. A team of researchers has now succeeded in rejuvenating the brain as part of the basic research — at least in mice, the exchange of liquor showed amazing effects.

According to a study, cerebrospinal fluid from young mice can improve memory of aged animals again. This is what was reported by an international research team after a number of experiments in the journal “Nature”. The group led by Tony Wyss-Coray of Stanford University in California has identified some of the proteins responsible for this “regeneration”. Two experts wrote in a Nature commentary that cerebrospinal fluid may help treat neurodegenerative diseases in the future. German experts are also impressed, even if the transmission of results to humans is questionable.

The research team, which also includes scientists from the University of Saarland, writes that brain aging is one of the causes of dementia, among other things, and places an enormous burden on society. The authors hypothesize that brain water (cerebrospinal fluid (CSF), also known as liquor) contains a number of substances important for brain cell maturation and function. However, the composition of the fluid changes with age: inflammatory proteins accumulate, growth factors decrease.

In the study, the team administered brain fluid from ten-week-old animals directly into the brains of aged mice, about 20 months old, for a week. Three weeks later, the group tested the mice’s memory — albeit with a fairly simple test.

Regenerated mice are more responsive

All animals were conditioned prior to treatment to associate sound and flashing light with an electric shock. After three weeks of treatment, cerebrospinal fluid-treated mice from young animals reacted more strongly to the warning sound and light than animals from the control group. From this, the team concludes that these mice better remember the sound and light that were previously foreshadowed by electric shocks. The team also found similar effects when elderly mice were given a drink of young people about 25 years old.

Further analyzes showed that cerebrospinal fluid had a particularly strong effect on a group of cells – called oligodendrocytes. These cells produce myelin, which coats nerve fibers and is important for the conduction of stimulation. In the case of multiple sclerosis, an autoimmune disease, the body’s defenses destroy the myelin sheaths in nerve cells, which can lead to disturbances in movement and cognition.

Other important items have been identified

According to the researchers, in old mice the cerebrospinal fluid in the hippocampus region of the brain, which is responsible for memory, caused oligodendrocytes (OPCs; oligodendrocytes) to mature and thus promote myelin formation. .

When examining substances in brain water, the team found growth factor Fgf17 (fibroblast growth factor 17), which older mice produce only in a limited amount. Even when the team gave the old mice this growth factor, their brain performance improved. Conversely, blocking the protein with antibodies in young animals impairs memory.

Fgf17 also occurs in humans and performs a number of functions. The authors emphasize that the Fgf signaling pathway is essential for the development of oligodendrocytes. In their commentary on “Nature,” Miriam Zawadzky and Maria Lehtinen of Boston Children’s write about a groundbreaking study of brain research and aging.

Results show potential in older brains

German experts were also impressed: “These are very exciting results because they show that even older brains still have the ability to regenerate a bit if they get the right signals,” says Dresden neurologist Gerd Kempermann, a spokesperson for the German Center for Neurodegenerative Diseases (DZNE). . “From a scientific point of view, it is especially exciting that a special group of brain cells, which has long been attributed a great potential for plasticity, interact with signals.”

However, it is largely unclear how this discovery can be transferred in detail to humans – not least because the very ancient mouse brain is several decades smaller than the ancient human brain. Kimberman stresses that direct treatment does not result from this. “But our knowledge of the ability to adapt and ‘regenerate’ the brain as we age is growing.”

Brain and age researcher Matteo Bergami also praised the study: “The presented experiments provide clear evidence of improved plasticity in OPCs and hippocampal brain circuits through supplementation of young cerebrospinal fluid or the specific agents contained in it,” confirms the expert from the University of Cologne. “If these findings are confirmed in further work, it will go beyond age-related cognitive decline as it may also have important therapeutic applications in demyelinating diseases such as multiple sclerosis.”

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