Rejuvenating liquor
Transfusion of cerebrospinal fluid from young mice improved memory in old ones
Polina Loseva, N+1
Not only blood can be transfused from young mice to old ones, but also liquor — a liquid that washes the central nervous system. A group of American scientists tried to do this, and it turned out that such transfusions help elderly mice to remember unpleasant stimuli. The authors of the work also claim that one specific molecule is significantly responsible for this effect — which, theoretically, could be used to treat dementia in humans. The article was published in the journal Nature (Iram et al., Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17).
Until recently, the idea of resisting aging with the help of "young blood" was very popular. It appeared from experiments on heterochronic parabiosis: older and younger mice were stitched together, and from such a neighborhood, old mice began to live longer and healthier. Then, in order to make the method applicable to humans, gerontologists switched from stitching animals to blood transfusion. It turned out that blood plasma, and sometimes even individual molecules from it, are enough for elderly mice to improve, for example, the condition of muscle tissue or even cognitive abilities.
Now transfusion of "young blood" is prohibited to people — at least in the USA, where there used to be several companies offering this service. But there are separate clinical trials that check whether it is possible to cure any age-related pathologies in this way, for example, Alzheimer's disease.
Meanwhile, a group of scientists led by a specialist in heterochronic parabiosis Tony Wyss-Coray from Stanford University Medical School decided to find out what would happen if transfused not blood plasma, but some other physiological fluid. And since even blood plasma, as it is clear from previous experiments, has an effect on the functioning of the nervous system, they suggested that an even stronger influence can be exerted by the cerebrospinal fluid, which also washes the ventricles of the brain.
To begin with, the scientists subjected the mice to a memory test. They electrocuted the elderly animals three times, simultaneously turning on a flashing light and a characteristic sound. After that, for a week, they were injected into the spinal canal or cerebrospinal fluid from young mice, or artificial cerebrospinal fluid (an analogue of a saline solution with salt concentrations characteristic of cerebrospinal fluid). And a couple of weeks later, the light bulb and sound were turned on again. As a result, in the control group, fading and fear were demonstrated by 18 percent of animals — the same as among those who did not receive electric shocks. And among the mice that were injected with "young liquor", there were twice as many frozen.
On the left: the design of the experiment with current, sound and a light bulb, on the right: the percentage of animals that have a memory of an unpleasant stimulus after transfusion of artificial (aCSF) or "young" (YM-CSF) liquor. Figures from the article by Iram et al.
The researchers then took tissue samples from the brains of experimental mice and compared gene expression in the control and experimental groups. They noticed that the genes associated with oligodendrocytes began to work especially strongly under the influence of the "young liquor" — these are auxiliary cells that form the myelin sheath of neurons.
Scientists have suggested that there could be more oligodendrocytes, that is, they began to divide. To test this, they injected labeled nucleotides into the brains of mice who were injected with liquor, which glow when they are embedded in a new DNA chain. And we found out that in general, cell division is almost not noticeable in the brain of elderly mice, but in the hippocampus — the area that is responsible for memory — the number of dividing cells has increased by 2.35 times.
I: percentage of dividing oligodendrocytes when treated with "young liquor" in different concentrations, M: division of oligodendrocytes (red) after treatment with artificial liquor (top) or "young liquor" (bottom)
Finally, scientists undertook to identify a specific substance from the liquor that could cause this effect. To do this, they treated the culture of oligodendrocytes with "young liquor" and measured gene expression after an hour. The gene encoding the regulatory protein SRF (serum response factor) reacted the most to the cerebrospinal fluid.
Then the researchers turned to the TRANSFAC database, from where they selected substances that presumably trigger the expression of the SRF gene. And among these substances, 35 were found that are found in the liquor. Having acted on the cells with them, they found that the Fgf17 protein affects SRF the most — and its concentration in the cerebrospinal fluid decreases with age.
The authors of the work suggest that oligodendrocytes in elderly mice under the action of Fgf17 are better preserved and produce stronger shells for hippocampal neurons, thereby preserving their viability — and this already affects the memory of animals. But they have to find out in detail what exactly Fgf17 does in the brain and what other processes it affects before talking about using it in humans — in the therapy of age-related dementia or some neurodegenerative diseases.
Earlier we talked about how blood transfusion helped mice cope with the consequences of a stroke. And also that its effect in some cases can be reproduced by simply diluting the plasma with a saline solution.
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