Epigenomics of depression
Depression is transmitted from fathers due to "supranomic" inheritance
It is believed that the state of depression is a consequence of hormonal imbalance in the brain resulting from the action of external factors in people with a genetic predisposition to this disease. However, the "depression genes" have not been identified. And only recently, researchers have discovered an alternative genetic mechanism that may be responsible for the development of this pathology.
Article by Wang et al. Sperm microRNAs conference depression susceptibility to offspring is published in the journal Science Advances.
Depression is one of the most common mental illnesses. It is known that it occurs as a result of an imbalance in the brain of a number of neurotransmitters, such as serotonin and dopamine, and is inherited, but the causes and mechanism of development of this disease are still largely unclear.
Recently, depression researchers have begun to pay special attention to epigenetic (supra-genomic) mechanisms that play the role of a bridge between genetic and environmental factors. In this case, the parents' life experience is reflected in the cellular genome not in the form of mutations, but in the form of DNA methylation, modification of histone proteins or changes in the number of free regulatory RNA molecules. And with the genetic material of germ cells, all these transformations can be directly transmitted to descendants.
Recently, a group of Chinese scientists studied, using the example of laboratory mice, exactly how such a transmission can occur. To induce a depression-like condition in male mice, they were subjected to moderate stress daily for 5 weeks in the form of food restrictions, unusual lighting, loud sounds, etc. As a result, the animals' body weight gain decreased, and tests showed an increase in emotions such as despair and hopelessness, as well as agedonia (a decrease in the ability to have fun). In addition, they have changed the activity of a number of genes involved in the work of nervous tissue.
Then, offspring were obtained from males with induced depression and healthy females, which under normal conditions did not show any deviations compared to control animals. But after exposure to chronic stress for two to three weeks, the children of depressed males also began to exhibit depressive behavior, and the profile of gene activity in their brains became similar to their father's.
In search of the mechanism of hereditary transmission of depression, scientists isolated a molecular fraction of small RNA from the sperm cells of depressed males, which was injected into the fertilized egg of healthy mice. The embryos were planted to surrogate mothers, who as a result gave birth to mice with already known depressive-like signs.
Without stopping there, scientists used synthetic molecules of 16 such microRNAs for similar purposes, which had the same effect as their natural "originals". But if synthetic antisense RNA molecules with a neutralizing effect were injected into fertilized eggs along with these microRNAs, then the cubs grew up healthy.
The results of this work suggest that depression is transmitted to descendants not through mythical "depression genes", but through a supra–genomic mechanism - an increase in the number of certain small regulatory RNAs. These inherited molecules seem to target key nodes of the gene networks of the embryonic brain, and as a result of their work, a special, "depressive" profile of gene activity is formed.
Fortunately, as a number of other experiments have shown, such hereditary depression threatens only the first generation. The "grandchildren" remain healthy, with an unchanged regulatory RNA profile – at least in mice. In addition, this work confirmed the possibility of successful treatment of depression using an advanced method – antisense therapy.
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