Alcohol and epigenetics
Gene therapy helped rats to give up alcohol
Sergey Vasiliev, Naked Science
Alcohol abuse often begins in adolescence, which is fraught with a lot of sad consequences. One of these effects is a change in brain function, in particular, the suppression of the activity of the Arc gene, which coordinates the work of the cellular skeleton of neurons, playing a huge role in memory and other functions. A few years ago, scientists showed that in the amygdala of people (and experimental mice) who consumed alcohol during adulthood, epigenetic "settings" change, blocking the work of the Arc gene. This manifests itself in increased anxiety and a tendency to alcohol throughout later life.
Continuing these studies, the team of University of Illinois Professor Subhash Pandey used genetic engineering tools in order to correct the Arc in laboratory animals addicted to alcohol. As it turned out, these manipulations can neutralize many undesirable manifestations, reduce anxiety and cravings for alcohol. Scientists write about this in a new article published in the journal Science Advances (Bohnsack et al., Targeted epigenomic editing ameliorates adult anxiety and excessive drinking after adolescent alcohol exposure), comparing the changes with a "rollback to factory settings".
The authors used the CRISPR-dCas9 system containing a modified Cas9 protein. As a rule, it is used for spot cutting of DNA in the area to which the sample corresponds — a small "guiding" RNA molecule. dCas9 also binds to DNA in the right place, but it is not able to cut it, allowing it not to change genes, but to perform more subtle manipulations. For example, to change their epigenetic settings and regulate their activity.
The experiments were conducted on rats that were "hooked" on alcohol during the growing up period corresponding to the human age of 10-18 years. As expected, in the future they showed increased anxiety and were less willing to examine unfamiliar objects. If such rodents were offered a choice of containers with clean water, sweetened or with the addition of alcohol, then they often reached for alcohol. However, after therapy with a new genetic system, the work of the Arc gene in their brain returned to normal, and then the behavior was "corrected". The animals no longer showed such anxiety and craving for alcohol.
Scientists have additionally confirmed the possibility of manipulating the Arc gene in "completely sober" rats. In them, with the help of CRISPR-dCas9, the activity of this gene was not stimulated, but, on the contrary, suppressed, which again led to the manifestation of the corresponding behavior. "Our results show that epigenetic editing in the amygdala makes it possible to normalize the psychopathological state in adulthood even after adolescent alcohol abuse," the researchers concluded.
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