Chromatin Research Can Explain Causes of Depression
Credit: Fotolia
An abnormal structure of chromatin, a complex of DNA strands and proteins tightly packed in the nucleus, could be the cause of depression, researchers from Warsaw say.
The scientists from the Nencki Institute PAS have now developed a 3D visualisation of chromatin structures to help explain the phenomenon.
A spokesman from the Institute said: “Today, depression is considered to be one of the main civilization diseases in the world. It is estimated that one third of the world's population suffers from it during lifetime.
“The debate about the causes of depression has been going on for over a hundred years. Today it is already known that causes include both external factors, such as prolonged stress or fear, as well as individual issues related to a person's innate predisposition.
“Studies of identical twins prove that the heredity of depression is 30-37 percent, depending on the parameters.”
Lead researcher Professor Grzegorz Wilczyński said: “The total length of DNA strands in humans is 2 meters, and the cell nucleus is only 10 micrometers (thousandths of a millimetre) in diameter. This means that the DNA strand must be extremely coiled.
“We think that the method of packing chromatin and its structure can affect the expression of genes, thus determining the functioning of cells, and as a result of the whole body.”
He added: “We want to examine how the neurons and astrocytes (glial cells) of patients differ from healthy cells in terms of the chromatin structure’.”
Until now, scientists did not know what the coiled bundles of chromatin in the cell nucleus look like in detail. The use of in situ hybridisation and an advanced electron microscope has allowed them to visualize the structures in three-dimensional form.
Professor Wilczyński's team's research results were published in the prestigious journal Nature Communications (https://www.nature.com/articles/s41467-020-15987-2?fbclid=IwAR2x9j9_atrIbG2gv_qfqPAs_D5k_9QrPKt-9jgAx_TEDme-A7zlp-noM1Y).
The research confirms the previous predictions for the structure of chromatin proposed by Professor Yijun Ruan from the Jackson Laboratory for Genomic Medicine in the US, who studies it with biochemical methods. Professor Grzegorz Wilczyński and Professor Yijun Ruan work together under a joint grant from the Human Frontier Science Program.
“In other diseases, for example in autism, there are known genetic defects that affect the structure of chromatin and people's behaviour. These include so-called coheinopathies.
“Professor Yijun Ruan has shown that there are chromatin loops that, for example, predispose people to asthma. By analogy, there could be other loops that predispose to depression.
“Specific enzymes are already being created that cut the loop of tangled chromatin. If we gave such a substance to a person, it could cut that interaction of chromatin that causes mental disorders.”
The project was carried out in cooperation with world-class scientists: Professor Yijun Ruan (Jackson Laboratory for Genomic Medicine, Farmington, USA), Dr. Werner Zuschratterem (Leibniz-Institut für Neurobiologie, Magdeburg, Germany) and Professor Ryszard Przewłocki (Institute of Pharmacology, Polish Academy of Sciences, Kraków), who provided inspiration to study the structure of chromatin in mental diseases.
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