Can Young Cerebrospinal Fluid Increase Cognition?

Breakthrough studies have shown that transfusion of cerebrospinal fluid (CSF) from young and old mice boosted memory in older animals.

CSF infusion triggered the fibroblast growth factor (FGF) signaling pathway, activated a transcription factor called SRF, and promoted the pathway leading to the proliferation and maturation of oligodendrosite, Tony Wyss- of Stanford University School of Medicine, California. Dr. Coray reported.Colleagues Nature.. Oligodendrocytes produce myelin, which supports neuronal signaling, leading to improved memory.

“The general message here is that the aging process is adaptable. Of course, thanks to this paper, it’s not new,” Wyss-Coray said in an interview. Today’s MedPage.. “But that adds to the idea that aging is a potential therapeutic target. It’s a process that we can start to better understand and manipulate.”

“Another message (more specific to the brain) is that improving the environment in which neurons live can actually significantly improve their function,” he added. “It is as important as, or sometimes even more important, to target the neuronal process itself.”

CSF is a clear fluid that soaks the brain, “the environment in which the brain swims,” ​​Wyss-Coray said. “It’s part of the brain’s direct environment, but we know very little about what its components do.”

Wyss-Coray et al. Injected CSF from 10-week-old young adult mice into the brains of 18-month-old adult mice for 7 days. Treatment improved memory recall in older animals with a fear-conditioning task in which they learned to associate small foot shocks with tones and flashing lights.

“Young CSF contains factors that help aged mice recall memory through oligodendrocyte maturation and hippocampal myelination,” researchers said. We have embarked on the field of aging, “says Dr. Maria Retinen and Dr. Miriam Zawajiki. / PhD candidate, both Boston Children’s Hospital, accompanied Commentary..

Previous studies have shown that fear conditioning in mice requires oligodendrocyte proliferation and myelin formation, and disruption of this process impairs memory. This raised the question of whether young CSFs could affect the proliferation and maturation of oligodendrocyte progenitor cells (OPCs).

“That’s right [the researchers] “Young CSF more than doubled the proportion of actively growing OPCs in the hippocampus of older animals,” Lehtinen and Zawadzki said. “Following this cellular change, myelin production occurs three weeks later.” Increased. The findings strongly suggest that young CSF improves cognitive performance in aged mice by regulating oligodendrocytes. “

When Wyss-Coray and colleagues studied primary OPC cultures, they found that serum response factors had the greatest increase in gene expression in response to young CSF treatment (“Srf), It encodes a transcription factor that initiates cell proliferation and differentiation.

When they screened for potential SRF activators in CSF, infusion of fibroblast growth factor 17 (Fgf17) was sufficient to induce OPC proliferation and long-term memory enhancement in aged mice, Fgf17. We have found that blockade of young mice impairs cognitive impairment in young mice.

“This suggests that Fgf17 not only can reproduce some of the useful effects of CSF from young mice, but also seems to require the young brain to function to its full potential,” Wyss-Coray said. Said.

This study was inspired by Wyss-Coray’s past studies. Blood from young mice It may restore memory function in older animals. He pointed out that looking at the aging of the brain as a whole may provide an opportunity to tackle intractable aging diseases such as Alzheimer’s disease.

“Our standard approach in medicine was to identify the condition, diagnose and monitor the condition, and try to intervene in the condition,” said Wyss-Coray. “But another approach may be to restore the function of the whole body and tissues and use it to figure out which key ingredients are involved in the improvement.”

“One step we haven’t really proved is whether we can reduce this to one factor or to several factors.” It’s natural to get the effect. You may only need a cocktail, but you can’t really analyze it. “