Is the cause of schizophrenia "defective" RNA?
Scientists have found out how voices arise in the head of schizophrenics
Scientists have discovered an unusual signaling RNA molecule in the human brain, the absence of which leads to the development of schizophrenia and the appearance of "voices in the head," according to an article published in the journal Nature Medicine (Chun et al., Thalamic miR-338-3p mediates auditory thalamocortical disruption and its late onset in models of 22q11.2 microdeletion).
"Two years ago, we discovered a specific chain of neurons in the brain, which is affected by well-known antipsychotic drugs. All of them, however, cause severe side effects. We isolated a micro-RNA molecule, which is a key element in the work of this chain of cells, and showed that the destruction of these micro-RNAs leads to the development of those disorders that are observed in schizophrenics," said Stanislav Zakharenko from St. Jude Children's Hospital in Memphis (USA).
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 most of them are young people aged 15 to 35 years.
There is no consensus among scientists yet 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 they have never been able to understand how mutations in these DNA regions cause schizophrenia and related effects – hallucinations or "voices in the head".
Zakharenko and his colleagues found that the latter effect can be caused by disturbances in the assembly of small RNA molecules known as miR-338-3p. This small sequence of genetic code, as scientists explain, controls the assembly and operation of Drd2 receptors on the surface of nerve cells that read dopamine – one of the main carriers of information in the brain and the pleasure hormone.
People with a mutation in the gene that is responsible for the assembly of this receptor or micro-RNA very often suffer from behavioral problems in childhood, and about 40% of them become victims of schizophrenia. All this prompted Zakharenko and his colleagues to check how both of these genome elements affect brain function by removing or blocking similar areas in the DNA of mice.
Experiments have shown that disabling miR-338-3p leads to the fact that the number of Drd2 receptors in neurons located in the center of hearing in the cortex of mice increased dramatically, which increased their sensitivity to dopamine molecules. As a result, their connection with the thalamus, the center for processing and distributing information, was disrupted, and the cortex began to work as if by itself.
This, according to scientists, can generate voices in the head, since information about perceived sounds usually undergoes primary processing in the thalamus and is probably cleared of noise and random signals.
As the experiment of Zakharenko and his colleagues showed, if the work of miR-338-3p is restored, then this cleaning resumes, which positively affected the behavior of mice, which, when new sources of sounds appeared, behaved extremely inadequately compared to normal individuals.
Accordingly, miR-338-3p molecules or the mechanisms that stimulate their production can be used for relatively safe treatment of schizophrenia or at least getting rid of its symptoms. In addition, a decrease in the concentration of miR-338-3p in old age may explain why older people are more likely to suffer from schizophrenia and other brain problems than young people, the authors conclude.
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29.11.2016