04 March 2019

Rejuvenation of neurons

Scientists have rejuvenated stem cells in the brains of mice for the first time

RIA News

European scientists have restored the ability of elderly mice to repair brain neurons by rejuvenating colonies of neuronal stem cells. The results of the first experiments of this kind were presented in the journal Cell (Kalamakis et al., Quiescence Modulates Stem Cell Maintenance and Regenerative Capacity in the Aging Brain).

"When we turned off the sFRP5 gene, the stem cells experienced some form of rejuvenation. As a result, the ratio of active and "sleeping" cells in the brains of elderly rodents became the same as in their young relatives. This brings us closer to the creation of drugs for neurodegenerative diseases," said Antonio del Sol from the University of Luxembourg (in a press release Scientists rejuvenate stem cells in the aging brain of mice – VM).

Until the 1960s, it was believed that no new neurons appeared in adult mammals, and their death was compensated by the redistribution of functions among the remaining nerve cells. In 1962, Joseph Altman showed for the first time, experimenting on rats, that adult rodents are undergoing the process of neurogenesis. Another 30 years later, Peter Eriksson's group discovered that new cells are also formed in the human brain.

Recent observations of the work of the human brain and other mammals show that some brain cells, for example, the olfactory center, are updated almost continuously, and in its other regions, including the hippocampus, the memory center, there are quite large colonies of stem cells that are presumably involved in neurogenesis.

In February last year, neurophysiologists from Zurich proved that this really happens by marking several stem cells in the brain of mice with the help of glowing proteins and tracking their growth. These observations immediately generated controversy among scientists – they showed that stem cells are rapidly depleted and almost completely disappear by old age, which contradicts many other observations.

Del Sol and his colleagues confirmed that this is indeed the case, and found out how to rejuvenate brain stem cells by analyzing the results of observations of the aging brain of mice using new computer algorithms.

"The problem is that stem cells live in niches where they constantly interact with other corpuscles, signaling molecules and various extracellular components. Their interactions are extremely difficult to simulate even on a supercomputer. Therefore, we began to think not about how the environment affects the cell, but about what state it will be in when it gets into a specific niche," the scientist continues.

Guided by this idea, scientists extracted stem cells from the brains of young and elderly mice and counted the number of active and "sleeping" bodies. After that, they studied and compared the contents of both types of stem cells, using this data to "calculate" the culprit of these changes.

It turned out to be the sFRP5 gene, one of the "brakes" of cell growth and their transformation into various types of tissues. With the onset of old age, its activity noticeably increases not in the stem cells themselves, but in the surrounding microglial cells and other brain tissues with depletion of the stem cell reserve and with increased inflammation.

This discovery prompted scientists to check what would happen if the work of this section of DNA was blocked in the brains of elderly rodents. To do this, they prepared immune bodies capable of neutralizing the proteins produced by sFRP5, and injected them into the body of mice for a week. This was enough to almost double the number of active stem cells both in a quiet life and in the event of serious brain injuries. Scientists hope that such experiments will help them understand how to rejuvenate the entire brain as a whole and protect it from the development of Alzheimer's and Parkinson's diseases.

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