Epigenetics: inherited memory?
Return to Lamarck?Alexey Levin, Voice of America
For example, a rat that has to switch to unusual food may gradually increase the volume of the stomach. A dog can be trained to salivate profusely in response to a call – as Pavlov once did in his classic experimental studies of conditioned reflexes. However, the offspring of such a rat will be born with a normal-sized stomach, and the puppies of a Pavlov-trained dog will not respond to calls with salivation. Similarly, the children of bodybuilders are born with normal muscles, and the children of astronauts do not show any special abilities to exist in zero gravity.
Changes in organisms that occur during life in response to changes in the environment are called acquired traits. Darwin's theory of heredity states that such changes are not transmitted to offspring. At the end of the 19th century, the German biologist August Weissmann set up a simple but convincing experiment that seemed to unequivocally confirm this principle. He cut the tails of young mice for twenty–two generations - nevertheless, all the mice were born with normal tails.
The prohibition on inheritance of acquired traits clearly follows from the provisions of classical genetics. According to this science, only changes in hereditary DNA structures, in other words, gene mutations, can be transmitted to offspring. Since acquired traits are formed without any genetic changes, they are not inherited. Everything is simple, clear and logical.
I must say that in recent years this picture has somewhat lost its former integrity. It turned out that such changes can also be inherited, in which the DNA structure remains completely stable. They are called epigenetic. Borrowed from ancient Greek, the prefix "epi" means "as well as", "in addition". Thus, epigenetic changes complement the actual genetic shifts. They manifest themselves, for example, in the modification of the activity of genes that themselves do not undergo any mutations. Such fluctuations in gene activity can occur under the influence of living conditions and pass on to descendants. However, unlike gene mutations, they are not too stable and disappear after several generations. Nevertheless, it looks like that some acquired signs or, in any case, their close analogues can still be inherited.
Similar effects have been noted not only in higher animals, but also in humans. In particular, there is reason to believe that epigenetic processes affect the risk of a number of diseases, including cancer. Some scientists even believe that epigenetics is associated with diseases stronger than genetics. It is no coincidence that last year the American National Institute of Health announced that it would spend a very impressive amount of $190 million over 5 years to study epigenetic mechanisms.
The phenomenon of epigenetic heredity brings to mind the first scientific theory of biological evolution, which historically preceded the Darwinian model. Its main provisions are set out in the book "Philosophy of Zoology", which was published exactly 200 years ago by the French biologist Jean Baptiste Lamarck (by the way, Darwin's great work "The Origin of Species by Natural Selection" was published in 1859, so this year is doubly jubilee for the theory of evolution). He claimed that acquired traits are inherited – in fact, this is what he explained the historical variability of biological species. However, the examples of such inheritance proposed by Lamarck turned out to be completely wrong. However, the idea itself has now unexpectedly revived, albeit in a new interpretation.
Recently, American scientists published the results of two experiments that demonstrated the possibility of epigenetic inheritance of skills acquired in the learning process (in the broad sense of the word). The first work appeared last month on the website of the journal Biological Psychiatry. Its authors, led by Professor of neuroscience at the University of Alabama J. David Sweat [J. David Sweat] worked with female rats. Even during pregnancy and after childbirth, the experimenters created severe stresses for them, because of which young mothers not only stopped caring for the cubs, but even offended them greatly. When the grown-up daughters of such rats gave birth to their own children, they also turned out to be bad mothers.
This effect has been noticed before, it was explained simply by the memory of a difficult childhood. However, Sweett and his colleagues found that it also manifests itself in cases when newborns are immediately taken away from evil mothers and planted with normal rats who take care of them as their own children. This can only be explained by the hereditary transmission of epigenetic changes – which ones, it remains to be seen.
Even more remarkable are the results of the second study, reported on February 4 by The Journal of Neuroscience. It was conducted by scientists from Boston Tufts University and Rush University of Chicago, led by Professor of biochemistry Larry Feig. They experimented with genetically engineered mice whose bodies did not synthesize two related proteins Ras-GRF1 and Ras-GRF2, which are involved in the transmission of intracerebral intercellular signals. Observations have shown that the deficiency of these proteins reduces the ability of the brain to form long-term synaptic contacts between neurons involved in the processes of memorization and learning (such interneuronal connections are called long-term potentiation). As expected, the memory of such mice, to put it mildly, left much to be desired.
It turned out, however, that this genetic defect can be temporarily corrected by proper upbringing in early childhood. When the protein–deficient mice grew up a little, the experimenters created, so to speak, an intellectually stimulating environment for them - they were given toys, provided conditions for physical activity and allowed to communicate with each other. As a result, after a couple of weeks, the animals' memory improved to normal levels. However, after stopping training, she degraded again, bad genetics took its toll.
This result is interesting, but, in general, quite predictable. However, Feig and his colleagues went further. When the mice trained in childhood and then returned to their normal state were several months old, they were allowed to become pregnant (females) or become fathers (males). Although the other parents in both cases were normal animals, the children were still born with the same gene defect – the mutation was dominant. But they behaved differently. The descendants of the males trained in childhood were no different in terms of memory from all other mice of the same line. On the contrary, the children of mothers who had undergone training showed improved memory during the first two months of life and only then fell into the usual forgetfulness. Their own offspring suffered from the same erosion of memory – from early childhood to old age.
The researchers also set up a control experiment. In theory, it can be assumed that the mother mice somehow passed on their experience gained during training to the cubs. Therefore, the experimenters immediately after birth transferred some of the mice to be raised by females who never went through training. However, even these animals did not suffer from impaired memory at first.
The authors of the work believe that in this case there was an undoubted epigenetic inheritance of acquired traits. According to Professor Feig, the mice's body reacted to the stimulating environment with some hormonal changes that restored their long-term potentiation. These changes were partly transmitted to their descendants of the first generation, but only on the maternal side. However, scientists do not yet know and do not guess how exactly this transfer was provided at the molecular level.
Of course, it would be very tempting to extrapolate the results of this experiment to humans. In fact, it's nice to assume that the girls' intellectual stimulation will lead to the fact that over time they will have particularly intelligent children. However, there are absolutely no grounds for such dreams yet. Mouse neurobiology is so different from human neurobiology that such an extrapolation would be pure quackery. Let's see what future research will bring.
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05.02.2009