Astrocytes (left) to reprogramming into neurons (right)Image: UC San Diego Health Sciences
Scientists at the University of California in San Diego found a way to restore the mouse brain damaged by Parkinson’s disease. To do this they programmed in specific brain cells — astrocytes — in the new neurons that replace the lost nerve cells, thus eliminating the symptoms of the disorder. About a new efficient method of the struggle with an incurable disease is discussed in an article published in the leading scientific journal Nature.
Parkinson’s disease is a severe neurodegenerative disorder characterized by loss of dopaminergic neurons in the black substance of the brain (Substantia nigra) that are involved in regulating motor functions and muscle tone. Dopaminergic neurons produce dopamine, a neurotransmitter, enables the transfer of signal to other neurons, which ultimately stimulates physical activity, reduces lethargy and stiffness. Currently there is no method for the treatment of Parkinson’s disease, although there are ways to slow down the loss of neurons.
In the new work, scientists have figured out how to force the brain to create new neurons. To do this, they lowered activity of a specific protein PTBP1 in astrocytes — zvizdovica cells that perform a number of helper functions: support neurons, provide the flow of nutrients to them, participate in the growth of nervous tissue, and in some cases are transformed into nerve cells to replace those killed.
It is known that the protein PTBP1 binds to RNA (intermediate products of gene activity) in the cell nucleus and thereby affect the expression of different genes. It is shown that blocking this protein alone is enough to turn certain types of cells in neurons. In the experiment, the mice were introduced molecule, which is similar to dopamine, but it is toxic to neurons, resulting in rodents have developed a chemically induced analogue of Parkinson’s disease.
In the black substance of the brain of animals also introduced safe AAV viruses that carried a small RNA molecule forming a hairpin (MC). These small RNAS are used to inhibit the activity of a particular gene, in this case, that encodes a protein PTBP1. Ten weeks later, 80% of astrocytes, which was introduced RK turned into neurons. After 12 weeks, 30-35 percent of the modified cells become dopaminergic neurons. Additional experiments showed that the introduction of small RNAS in other areas of the brain led to the emergence of other types of neurons, indicating the existence in astrocytes of different genetic programmes depending on their location.
Finally, dopaminergic neurons had axons (long processes), which are “intertwined” in the nigrostriatal nerve pathway to the brain, restoring its normal function and dopamine levels. That is the nigrostriatal path is responsible for the connection of the black substance with physical activity, so the mice disappeared signs of the disease. According to scientists, the results will help to develop effective approaches in the treatment of Parkinson’s disease.
Video, photo All from Russia.