A colorized transmission electron microscope image of an oligodendrocyte (blue) surrounded by cells that it coated in myelin (red outlines).
A colorized transmission electron microscope image of an oligodendrocyte (blue) surrounded by cells that it coated in myelin (red outlines).

Brain Fluid from Youngsters Gives Old Mice a Memory Boost

A growth factor found in the cerebrospinal fluid of young mice triggered the proliferation of myelin-making cells when injected into the brains of older mice.

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Dan Robitzski

Dan is a Staff Writer and Editor at The Scientist. He typically works on the news desk and joined the team in 2021. He has a background in neuroscience and earned his master's in science journalism at New York University.

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May 11, 2022

ABOVE: A colorized transmission electron microscope image of an oligodendrocyte surrounded by myelin-coated cells © ISTOCK.COM, JOSE LUIS CALVO MARTIN & JOSE ENRIQUE GARCIA-MAURIÑO MUZQUIZ

Silicon Valley startups claiming that injections of young people’s blood could have health benefits for the elderly or sick have risen and fallen, without much in the way of actual science backing their claims. The idea gets a revamp in mouse research published today (May 11) in Nature, which suggests that injecting cerebrospinal fluid (CSF) from younger into older mice can rejuvenate the memory of the recipients under specific conditions.

Cerebrospinal fluid has an important dual role: it cushions the brain and provides nutrients as it flows in and around the brain’s cavities and folds. In the study, 18-to-25-month-old mice that had the CSF of 2-to-3-month-old mice injected directly into their brains outperformed controls on a fear conditioning memory task. The study authors say that’s thanks to the growth of new oligodendrocytes, which support other brain cells by producing myelin, the insulation that shields neurons’ axons.

“Oligodendrocytes are unique because their progenitors are still present in vast numbers in the aged brain, but [those progenitors] are very slow in responding to cues that promote their differentiation,” study coauthor Tal Iram, a Stanford University School of Medicine neuroscientist, tells The Scientist over email. “We found that when they are re-exposed to young CSF, they proliferate and produce more myelin in the hippocampus,” a brain region associated with memory formation and retention.

This is an interesting and unique pathway compared to much of the literature on memory formation.

—Janine Kwapis, Penn State University

Prior to their injections, the mice were trained to associate a flashing light and a tone with an electric shock on their feet. After training, the older mice were infused with a steady drip of either young or artificial CSF (water mixed with sodium, potassium, and other ions) over the course of one week and were tested with the memory task another two weeks after that. Iram and her colleagues found that the animals that received the young mouse CSF froze in response to the light and tone more often than controls, indicating that they better remembered the electrical shocks. The animals that were injected with the artificial CSF had comparable freezing rates to age-matched mice that didn’t receive CSF injections at all.

See “Blood Transplants from Active Mice Give Brain Boost to Others

Janine Kwapis, a memory and aging researcher at Penn State University who didn’t work on the study, says in an email that she found it “pretty mind-blowing” that CSF injections improved cognition in older animals, even though “the idea of a therapeutic young-to-old injection isn’t new.”

“What’s really novel here is the identification of oligodendrocytes as a key player in brain age,” she adds. “Although research has historically focused almost exclusively on neurons as being central to brain function, more recent research has begun to appreciate the key roles played by glia cells (like oligodendrocytes), which seem to be just as important to brain function as neurons.”

In a follow up experiment, the researchers dissected brain sections shortly after injecting the young mouse CSF into the older mice and analyzed RNA production to reveal the molecular pathway responsible for the improved memory. They found that, relative to controls, the treated mice had increased levels of serum response factor (SRF), a transcription factor that increased proliferation of oligodendrocyte progenitor cells. A comparison of samples from 3- and 25-month-old animals showed that levels of SRF RNA naturally decrease in the mouse hippocampus with age. However, their analysis of CSF-treated mice shows that a compound called fibroblast growth factor 17 (Fgf17), which the researchers found in the young mice’s CSF, boosts SRF levels. The team also found that injecting Fgf17 alone had the same effects on older mice as the young-CSF injections, and that blocking the growth factor’s action in younger mice impaired memory.

“This is an interesting and unique pathway compared to much of the literature on memory formation,” Kwapis says.

Iram says she and her colleagues are “currently investigating the potential translational aspects of this study,” although other experts tell The Scientist that its relevance to humans is murky at best.

“It’s unlikely that a single blood transfusion (or CSF transfusion) from a young person . . . will have a lasting rejuvenation effect in an older person,” Kwapis says.

According to Gabriela Popescu, a biochemist at the University of Buffalo Jacobs School of Medicine & Biomedical Sciences who studies the neuroscience of memory but didn’t work on the new paper, the study is another instance of work that—wrongly, she says—frames aging as a disease in need of a cure.

“I think it’s wrong to sell science this way,” she tells The Scientist, referring to studies that imply there’s a straightforward way to reverse aging, memory loss, or other common sources of health-related anxiety.

See “Opinion: Biomarkers of Longevity Not Ready for the Clinic

Despite her reservations, Popescu says that the paper’s observations are interesting and “a good fact to know.” Going forward, Kwapis says it would be interesting to see if the same pathway mediates other forms of memory and learning, especially those that are thought to involve other brain regions like the amygdala and various cortices.

“It would be helpful to know whether these young CSF infusions also improve memories that are less salient and stressful and are more typical of the common ‘everyday’ types of memories that are most susceptible to age-related decline,” she says.