15 April 2014

RNA transmits the effects of childhood stress to descendants

Psychological traumas are inherited with the help of RNA

Kirill Stasevich, CompulentaFrom time to time, we report the discovery of another case of epigenetic coding, when a certain sign changes not because the sequence of nucleotides in DNA has been transformed, but because of some incident with proteins serving a particular area of DNA, or nucleotides in it, which, while remaining in their places, have 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 of regulation of genetic activity serve as intermediaries between genes and changing living conditions, but the results of this mediation, as they say, cannot be cut down with an axe.

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 DNA packaging proteins, we can make memory more plastic, editable. Another example is the influence of living conditions in early childhood on the pattern of epigenetic modifications, and these modifications, as it was said, remain with a person almost for life.

Moreover, it is believed that epigenetic modifications can not only stay with us forever, but also pass into the next generations. In the case of obesity, for example, many researchers believe that metabolic disorders leading to obesity are fixed in epigenetics, and then transmitted through the male line. That is, if the father ate incorrectly and disrupted his metabolism, there is a possibility that his children will be overweight, even with a completely healthy diet.

However, in the case of epigenetic inheritance, there is one problem: it is not entirely clear how such modifications can pass from parents to descendants. In plants, this mechanism is more or less clear, but in animals, germ cells get rid of epigenetic modifications, and then how is the epigenetic code inherited? (However, it is worth noting here that recently it was possible to find epigenetic modifications that, despite everything, remain in the germ cells at all stages of their maturation.)

Perhaps a new study (Gapp et al., Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice), published in Nature Neuroscience by specialists from 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 inheritance of behavior in mice. To do this, the animals were caused childhood trauma: while they were young, they were taken away from their mothers for a while every day for two weeks. This unpredictable stress hit both the cubs and the females, who were also put in a tight tube for a while.

When 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 (an ordinary mouse, of course, would avoid such places). Such 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.

But most importantly, these changes in behavior and metabolism were inherited. When stressed mice in childhood were crossed with ordinary mice, their offspring also showed indifference to danger, signs of depression, their body also did not handle glucose normally. And all this was passed on not only to children, but also to grandchildren, that is, also to the second generation.

Trying to determine the molecular mechanisms of inheritance, scientists found that sperm cells, blood serum and hippocampus in mice with childhood trauma and in ordinary rodents differ in the level of some microRNAs and PIWIRNAS (a special kind of non-coding regulatory RNAs). Stress changes in regulatory RNAs were observed both in children of stressed mice (especially in the hippocampus and serum) and in their grandchildren.

To make sure that it was still regulatory RNAs, the researchers took these RNAs from the sperm cells 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, as they grew up, the mice showed the same behavioral and metabolic features as the direct descendants of stressed parents.

That is, a child's psychological trauma can be felt for two more generations, and regulatory non-coding RNAs work as carrier molecules here, 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 RNA of childhood stress comes into the embryo along with the sperm.

Now scientists face such a task: it is necessary to understand exactly how the regulatory RNAs inherited affect the development of the metabolic pathways of a new organism and its brain. Having found 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.

Prepared based on the materials of the Swiss Higher Technical School of Zurich: Hereditary trauma.

Portal "Eternal youth" http://vechnayamolodost.ru15.04.2014

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