Science

The brain fluid of young mice rejuvenated the brains of old mice

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Scientists have been trying for decades to counter the devastating effects of aging on our brain capabilities, in addition to the effects on the rest of the body. Not to mention that neurodegenerative diseases growing with the aging of the world population. The immediate environment of our nerve cells has been carefully studied for some time in an attempt to understand its mechanisms. Recently, a group of American researchers identified a protein in the cerebrospinal fluid that stimulates cells to maintain brain function. This could lead to future treatments for neurodegenerative diseases.

Aging and age-related cognitive decline affect up to a quarter of adults over 60. A healthy diet and regular physical activity can help prevent this decline, but there is currently no treatment available to reverse it.

Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies aimed at slowing brain aging. This systems approach is used to understand the brain in its environment, its functioning and mechanisms.

From this point of view, cerebrospinal fluid (CSF) is the immediate environment of brain cells. This fluid bathes the tissues of the brain and spinal cord of all vertebrates, supplying them with nutrients. It is necessary for normal brain development. Physicians often use it as an indicator of brain health and as a biomarker for neurological disease. But as mammals age, cerebrospinal fluid loses some of its effectiveness, and these changes could affect memory-related cells.

That’s why Tal Iram, a neuroscientist at Stanford University in California, and his colleagues investigated whether young cerebrospinal fluid injected into older adults could improve degraded brain functions, including memory. That seems to be the conclusion of their study, published in the journal Nature.

Significant improvement in memory

The CSF work builds on earlier work by Wyss-Coray showing that plasma from young mice can restore memory function in old rodents. But the technical challenge here was much more difficult: namely, extracting the cerebrospinal fluid and then reinjecting it into another brain. It took almost a year to bring the necessary technology into play. The collection is extremely difficult and must be done with precision. Any contamination with blood destroys the fluid. Not to mention that pressure in the brain is due to a delicate balance, so the infusion must be slow and delivered to a precise location in the brain: the cerebral ventricle.

Tal Iram and his team’s second step was to give the aging mice a memorable experience to test their memory. The team of scientists gave 20-month-old mice three small electric shocks to one paw in tandem with several flashes of light and sound to create a connection between light and electric current.

The researchers then infused the brains of a group of 8 mice with cerebrospinal fluid from 10-week-old mice, while a control group of 10 mice received artificial cerebrospinal fluid. Three weeks later, the mice were presented with the same visual and auditory stimuli, but this time without shock, recreating the context of fear without actual action. Nearly 40% of mice injected with young CSF remembered the shock and froze in fear, while only about 18% of mice given artificial CSF froze. The results show that young CSF can, to a certain extent, restore brain abilities degraded with age.

Study co-author Tony Wyss-Korey, a neuroscientist at Stanford, said in a statement accompanying the study: “The broader implication is that the brain is still malleable and there are ways to improve its performance. Not everything is lost”.

Better isolation of brain wiring and key protein

The researchers then wanted to understand the mechanism behind the promising results they got. You should know that the hippocampus is the memory control center of the brain: it is responsible for creating, storing and recalling memories. That’s why the team focused on this structure to try to better understand how young cerebrospinal fluid can improve memory function in aging mice.

Thus, they found that the structure activates genes associated with cells called “oligodendrocytes.” Oligodendrocytes form a myelin sheath around the tails of neurons. Wiss-Korey explains in simple terms: “This is the coating that covers the “threads” in the brain. And, like wire insulation, this sheath promotes conduction.”

In particular, CSF helps to generate more early-stage oligodendrocytes, the progenitor cells of oligodendrocytes. The equation is simple: making more cells that isolate nerve connections helps keep the brain working.

The scientists also isolated a protein in the fluid that, according to another analysis, could be a compelling candidate for improving memory: fibroblast growth factor 17 (Fgf17). Fgf17 infusion had a similar memory recovery effect as CSF infusion. In addition, administration of antibodies blocking Fgf17 function to mice disrupted the ability of rodents to remember. Wyss-Coray and Iram have applied for a patent on their findings regarding Fgf17.

Iram and Wyss-Coray conclude: “Fgf17 and CSF appear to be promising elixirs for brain health, but studying the ways CSF interacts with oligodendrocytes and how these cells are involved in memory will be important to improve our understanding of brain aging.

The procedure used, which is very delicate, can pose challenges for use in humans, whether in terms of safety, complexity, and discomfort (painful lumbar punctures, which are still considered “invasive” by medical professionals) or even in terms of ethics (puncture and then needle infusion). fluid from a young person to an elderly patient). Among the challenges is also understanding what other cerebrospinal fluid proteins may be involved and how to exploit their effects without causing obvious problems.

Nature

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