The psychological stress experienced by an individual in childhood can affect behavior and metabolism in the next two generations, for which special regulatory RNAs that travel with sperm are to be blamed.
From time to time we report on the discovery of another case of epigenetic coding, when a certain sign changes not because the sequence of nucleotides in DNA has changed, but because of some incident with the proteins serving a particular region of DNA, or nucleotides in it, which, while remaining in their places, acquired chemical modifications. After that, the activity of the gene does not just change, but changes for a long time, as if the nucleotide sequence was indeed rewritten.
Epigenetic mechanisms regulating genetic activity serve as mediators between genes and changing living conditions, but the results of this mediation, as they say, cannot be cut out with an ax.
One of the most striking examples of a strong epigenetic effect on the body is the connection between memory and histone modifications: by influencing what happens to these proteins - DNA packers, we can make memory more plastic, accessible to editing. Another example is the influence of living conditions in early childhood on the pattern of epigenetic modifications, and these modifications, as has been said, remain with a person for almost his entire life.
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Moreover, it is believed that epigenetic modifications can not only remain with us forever, but also pass on to future generations. In the case of obesity, for example, many researchers believe that metabolic disorders that lead to obesity are anchored in epigenetics and then transmitted through the male line. That is, if a father ate improperly and disrupted his metabolism, there is a possibility that his children will be overweight, even with a 100% healthy diet.
However, in the case of epigenetic inheritance, there is one problem: it is not entirely clear how such modifications can be passed from parents to descendants. In plants, this mechanism is more or less clear, but in animals, the germ cells get rid of epigenetic modifications, and how, then, the epigenetic code is inherited?.. (However, it is worth noting that recently it was possible to find epigenetic modifications, which, despite that remain in the germ cells at all stages of their maturation.)
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Perhaps a new study published in Nature Neuroscience by specialists at the University of Zurich (Switzerland) will help clarify the situation with epigenetic inheritance in animals. Isabelle M Mansuy and her colleagues studied the molecular mechanisms of behavior inheritance in mice. To do this, the animals caused childhood trauma: while they were small, they were taken away from their mothers for a period of two weeks every day. This unpredictable stress hit both the cubs and the females, who, moreover, were put in a tight pipe for a while.
As the stressed cubs grew up, the researchers noticed that they were more indifferent to danger: for example, they were less afraid of open and well-lit spaces than others (a common mouse, of course, will avoid such places). This indifference to risk is considered a sign of depression; it can be said that depressed adults grew out of stressed cubs. In addition, there were differences in glucose metabolism, that is, stress at an early age continued to affect not only behavior, but also the metabolism of adult animals.
Most importantly, these changes in behavior and metabolism were inherited. When stressed in childhood mice were crossed with ordinary mice, their offspring also showed indifference to danger, signs of depression, their bodies also did not handle glucose normally. Moreover, all this was passed on not only to children, but also to grandchildren, that is, also into the second generation.
Trying to determine the molecular mechanisms of inheritance, the scientists found that sperm, blood serum and hippocampus in mice with childhood trauma and in normal rodents differ in the level of some miRNAs and piwiRNAs (a special type of noncoding regulatory RNA). Stress changes in regulatory RNAs were observed in children of stressed mice (especially in the hippocampus and serum) and in their grandchildren.
To make sure that it was still a matter of regulatory RNAs, the researchers took these RNAs from the sperm of mice with childhood trauma and injected them with someone else's fertilized egg (in other words, the germ cells themselves did not experience any stress in this case). After that, the egg was implanted into the female and waited for the cubs, conceived in such a cunning way, to be born. As you might guess, growing up, the mice showed the same behavioral and metabolic characteristics as the immediate descendants of stressed parents.
That is, children's psychological trauma can backfire for two more generations, and regulatory noncoding RNAs work here as carrier molecules, which, along with histone modifications and DNA methylation, are considered one of the main conductors of "epigenetic forces." Note that in this case we are again talking about the inheritance of the epigenetic code in the male line: the RNAs of childhood stress enter the embryo together with the sperm.
Now scientists are faced with the following task: it is necessary to understand how exactly the inherited regulatory RNAs affect the development of the metabolic pathways of the new organism and its brain. By finding out the details of this mechanism, we will find out whether it participates in the formation of other types of behavior and whether it works in humans.