Small RNAs control psychiatric diseases

The high genetic similarity between schizophrenia and bipolar disorder translates into over a 70% overlap of disease-specific changes in brain cells. A study revealed gender-specific differences in these changes.

Gender-specific processes in schizophrenia and bipolar disorder observed

Only recently have researchers found a high genetic similarity of the psychiatric diseases schizophrenia and bipolar disorder, whose disease-specific changes in brain cells show more than a 70% overlap. A study has now revealed gender-specific differences in these changes.

A special role is probably played by microRNAs, a special group of these small nucleic acid molecules, which are known for their comprehensive control of gene expression in all human cells. If a gene is the target of such a microRNA, this can lead to a significant expression restriction. "The problem here is the enormous variety of possible combinations," said Sebastian Lobentanzer, the lead author of a recent study on the issue. "Humans possess about 2,500 such microRNAs, and a single one can affect hundreds, maybe even thousands of genes," he added.

For this reason, the scientists used a combination of RNA sequencing and bioinformatics to study gene expression in the brains of patients as well as human nerve cells in cell culture. They found that the expression of genes of the immune system differed between men and women, particularly with regard to cytokines, the messenger substances of immune cells. In cell culture experiments with male and female neuronal cells, the researchers used substances from this class and found that the nerve cells converted into cholinergic-type neurons.

By sequencing the microRNAs at several points in time during this process, a comprehensive picture of the microRNA interface between the immune system and the nerve cell could be obtained. The scientists identified 17 families of microRNAs, some of which were sex-dependent, and created a comprehensive network of 12,495 affected genes. The most influential of these microRNA families were determined through a multi-stage selection process and confirmed in dedicated experiments. Thus, the two sex-specifically expressed families mir-10 and mir-199 were identified as interfaces between cytokines and cholinergic functions.

Due to their high genetic complexity and their inaccessibility to conventional forms of therapy, psychiatric diseases are an important field for new therapeutic approaches.

On the one hand, the present study showed cellular parallels to the long-known but yet unexplained clinical differences between diseased men and women. On the other hand, mechanisms based on small RNA molecules could point the way forward by influencing a large number of disease-relevant genes; a promising approach in the search for alternatives to traditional psychotropic drugs. "Studies such as ours, which make it possible to show all interactions of microRNAs, are the first step on the way to developing new drugs," said Lobentanzer.

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