Is the cause of schizophrenia not just in neurons?
Human and mouse chimeras helped scientists find the "secret conductor" of schizophrenia
The main cause of the development of schizophrenia and a number of other mental disorders may not be breakdowns of individual genes in neurons, but mutations in the DNA of their "servants", scientists say in an article published in the journal Cell Stem Cell (Windrem et al., Human iPSC Glial Mouse Chimeras Reveal Glial Contributions to Schizophrenia).
"We have shown that disorders in the work of glial cells are the cause of the development of schizophrenia, the first signs of which begin to manifest themselves in childhood. The inability of these cells to cope with the tasks assigned to them, including the establishment of a full–fledged system of connections between neurons, is the main cause of the development of the disease," says Steven Goldman from the University of Copenhagen (in a press release, Fault Support Cells Disrupt Communication in Brains of People with Schizophrenia - VM).
Today, about 24 million people on the planet suffer from schizophrenia. According to WHO statistics, every seventh person out of a thousand is schizophrenic, and many of them are young people aged 15 to 35 years.
At the moment, there is no consensus among scientists on how such disorders arise and how they should be properly treated. In recent years, geneticists have found several dozen genes that are relatively poorly associated with schizophrenia, but scientists have not been able to understand before this discovery how mutations in these DNA regions cause schizophrenia, and how the consequences of these mutations can be eliminated.
Goldman and his colleagues discovered an unusual link between schizophrenia and the work of auxiliary brain cells by observing the behavior of mice whose glial cells were completely replaced by their human counterparts.
To obtain such rodents, scientists created several chimera embryos, some of whose cells were obtained not from the mother mouse and the father mouse, but from people suffering from severe forms of schizophrenia. By manipulating the behavior of these stem cells, biologists were able to grow mice that have the intelligence of rodents, but at the same time have human glial tissue.
Using such rodents, Goldman's team began to test how various mutations associated with the development of schizophrenia today will affect the work of the "human" part of the brain of mice and whether these changes will affect the functioning of neurons.
As these experiments have shown, the appearance of breakdowns in the DNA of glial cells in some cases led to serious problems in the formation of chains of neurons even during the growth of the embryo, as well as problems associated with an insufficient number of connections between them.
For example, DNA damage in some glial cells associated with the work of "isolation" of neurons led to the fact that they began to block random impulses produced by nerve cells much worse, and interfered with, rather than helped the formation of connections between neurons.
As a result, a number of problems usually associated with schizophrenia arose – such mice avoided contact with rodents unfamiliar to them, did not like sweet food, behaved strangely during standard intelligence tests and showed a high level of anxiety.
All this, according to scientists, indicates that many cases of schizophrenia arise due to disturbances in the work of not neurons, but their "neighbors", who were not previously associated with this disease. The study and suppression of these disorders in the glia, according to Goldman, can pave the way to the creation of the first real cure for schizophrenia.
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21.07.2017