Crispr tapered stem cells in the brain of mice

CRISPR-Studien zeigen, wie ein bestimmtes Gen bei Mäusen die Jugendlichkeit von Gehirn-Stammzellen wiederherstellt und deren Wirkung auf neue Neuronen steigert.
Crispr studies show how a certain gene in mice restores the youthfulness of brain stem cells and increases their effect on new neurons. (Symbolbild/natur.wiki)

Crispr tapered stem cells in the brain of mice

Information on the preservation of the Regenerative cells in the brain , which remain young and energetic in old age, were discovered by using the crispr genetics on mice 1 .

The age makes it difficult for the stem cells in the brain to produce new cells. However, the authors of the study found that a reduction in the activity of a certain gene this Stem cells rejuvenated, which made it possible for them to multiply and provide the brain with new neurons.

This gene regulates the glucose consumption of the stem cells, a sugar that is crucial for cell metabolism. The results of mice go well with the emerging image of studies on post -mortal human brains. These studies have also shown that age influences the metabolism in the brain, says Maura Boldrini, neuroscientist and psychiatrist at Columbia University Irving Medical Center in New York City, which was not involved in current research. "Your metabolism is probably less efficient than before," she adds, noting that both the human results and the mouse study, which was published in Nature today, "open new ways for potential therapy approaches."

a youthful brain

The role of Neural stem cells in the human adult brain is controversial. Boldrini and others have published evidence that new neurons in the hippocampus, an area of ​​the brain that are important for learning and memory, are formed 2 . Your team is now investigating whether the production of new neurons in people with Alzheimer's or psychiatric diseases is changed. However, some researchers report that they have not found any evidence that adults form new neurons in the hippocampus. "These controversy continue to take place," says Boldrini.

The picture is clearer for mice. In a region of the brain, which is referred to as sub -fertricular zone, neural stem cells can produce neurons and other cell types. These young cells then hike to the olfactory piston, which is responsible for the sense of smell . A constant supply of fresh neurons for the olfactory piston makes sense for mice, since they are very dependent on their sense of smell in order to perceive changes in their environment, says Anne Brunet, geneticist, who is concerned with aging at Stanford University in California and is the author of the new study.

If mice get older, these stem cells become less active. Brunet and her team decided to find out why. The researchers used Crispr-Cas9 Gentechnology to systematically disrupt 23,000 genes, and then tested the effects of each disturbed GES on neural stem cells that were taken from young and old mice and bred in the laboratory.

neuronal support

The screening resulted in 300 genes that could play a role in ageing the neural stem cells. The researchers further restricted the pool by using Crispr-Cas9 to disturb some of these genes in cells of the sub-fertricular zone of living young and old mice. The authors then checked the animals of the animals and identified a selected group of more important genes. The disturbance of this genes increased the production of neurons by stem cells in old animals, but did not affect the stem cells of young animals.

Such a gene, called SLC2A4, codes for a protein that imports glucose into the cells. The disruption of this gene reduced the glucose absorption of the cells and increased their propagation.

This result correlates with previous studies that have found a connection between sugar metabolism and aging, says Saul Villeda, neuroscientist at the University of California, San Francisco. For example, researchers recently reported that a diabetes medication Age-related cognitive breakdown in monkeys can counteract . But the latest result is particularly important because it indicates a specific protein that plays a key role and could be targeted in future studies, he says.

Even if the role of neuronal stem cells in adult people is questionable, the results provide decisive information for the development of cell therapies that could one day treat neurodegenerative diseases.

  1. Ruetz, T. J. et al. Nature https://doi.org/10.1038/S41586-024-07972-2 (2024).

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  2. Boldrini, M. et al. Cell Stem Cell 22, 589–599 (2018).

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  3. Sorrells, S. F. et al. Nature 555, 377–381 (2018).

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