In the future, these studies may become the basis for the treatment of Alzheimer's and Parkinson's diseases.
What happens to the work of mouse brain nerve cells during aging was modeled for the first time in the world by specialists from the Department of Neurotechnology at the Institute of Biology and Biomedicine of Lobachevsky University. According to the authors of the work, the time will come when the disruption of the brain can be reversed with the help of light signals aimed at fading astrocytes. The details of the study are in an interview with Elena Mitroshina, Associate Professor of the Department of Neurotechnology, Doctor of Biology.
Elena Mitroshina on the background of the image of astrocytes. Photo: UNN Press Service (Andrey Skvortsov)
Scientists have long wanted to understand what causes brain aging, what happens in it over time and leads to dementia and memory loss. The main object of study, of course, are brain cells – neurons and astrocytes, glial cells.
“Our laboratory is studying how not individual cells work, but entire networks of nerve cells, including not only neurons, but also glial cells, which are represented by astrocytes — star-like cells with processes,” says Elena Mitroshina. – We recently completed the first stage of a unique study of a network of such astrocytes grown from cells of the mouse cerebral cortex.
< p>– It used to be that astrocytes, which are located between neurons, simply help them, nourish them, and are a structural support for them. However, not so long ago, experts realized that they are involved in the regulation of the work of neurons, as well as in the transmission of information along with biologically active substances – neurotransmitters. In addition to transmitting signals to neurons, astrocytes also communicate with each other. True, this system is arranged a little differently – these are not electrical, but chemical signals. That is, cells transmit information to each other through the so-called calcium waves.
A calcium wave is a sequential transmission of calcium signaling ions by astrocytes to each other. This feature is characteristic of the glial cells of the brain.
The peculiarity of our work was to study the mechanism of “communication” of astrocytes and how this communication changes with aging.
– It was a unique model work of its kind, not even on animals, but on the culture of their cells. We grew mouse astrocytes in a laboratory petri dish and looked at how they communicate with each other via calcium waves when they are young and when they are old. Naturally, the experiment lasted a very long time – we cultivated, grew cells and waited for them to begin to show signs of aging. It took half a year…
– You can say that. Considering that a mouse lives on average for about 1.5 years, our experimental model was quite old, that is, we simulated aging by sequentially studying it under a microscope using calcium imaging.
Astrocytes (highlighted in red) under a microscope. Photo: UNN Press Service (Andrey Skvortsov)
“We found that over time, astrocytes began to transmit fewer signals to each other. The analysis of such data is a very difficult task, and in this we were helped by cooperation with mathematicians of our university, primarily with Mikhail Krivonosov. We assume that in addition to a decrease in signaling between astrocytes, their interaction with neurons also decreases, and in general, all this leads to brain dysfunction. Therefore, the next stage of our work will be to find a mechanism for maintaining this “communication” so that astrocytes continue to work like young ones with age.
– We want to use methods of optogenetics to rejuvenate the signaling system of the brain. This is a modern genetic engineering technology: a special light-sensitive protein is created, which is integrated into the cell membrane and creates a channel for the passage of calcium ions into the cell. The channel is controlled by light of a certain wavelength. Further, the astrocyte activated in this way transmits information to neighboring astrocytes.
– Optional. This is the beauty of astrocytes – they are very friendly guys who interact well with each other. If you activate one or more of them, then they will transmit a signal to all the others.
– If our most optimistic assumptions are confirmed, even an operation will not be needed. This will be a separate transcranial (through the skull) injection, providing the cell with the very necessary light-sensitive protein that we talked about above.
– At the current stage of development of technologies in order for the protein to react into the light, it is necessary to deliver its source – optical fiber – closer to the cells. They don't do it in public. In the case of mice, a special cannula is implanted into the brain, a capsule through which an optical fiber is passed to the cells. But technologies are developing – experts are working on creating the most light-sensitive proteins that would react to light during transcranial stimulation, without implanting an optical fiber into deep brain tissues.
This is the future. In the meantime, scientists are testing the optogenetic method on cultures of those same mature mouse brain cells. If they get a good result, they will switch to the animals themselves, and then to humans. Who knows, maybe we are at the origins of a technology that will allow our civilization to at least forget what dementia and age-related learning problems are. In the future, it can also become the basis for the treatment of Alzheimer's and Parkinson's diseases.