Stress in infants leaves a lifelong mark on genes
Scientists from the Institute of Psychiatry named after Max Planck (Germany), working under the guidance of molecular biologists Chris Murgatroyd (Chris Murgatroyd) and Dietmar Spengler (Dietmar Spengler), found that epigenome changes are at the heart of the long-term negative effects of stress on physiology and behavior in the early stages of life. (Epigenomics is a relatively young science that studies not the complete set of genes of an organism in the form of nucleotide sequences, but gene expression – the intensity of synthesis of the corresponding proteins.)
The authors demonstrated that early stress exposure induces epigenetic changes in a special regulatory region of the genome, which affects the expression of the hormone vasopressin, which plays an important role in regulating mood and cognitive abilities in adulthood. The results of the work were published on November 8 in the preliminary issue of the on-line version of the journal Nature Neuroscience in the article "Dynamic DNA methylation programs persistent adverse effects of early-life stress".
According to the generally accepted hypothesis, the environment influences mental health through changes in the physical properties of the genome, which, in turn, affects gene expression. Indeed, according to the results of the study, the features of DNA methylation – one of the most intensively studied epigenetic mechanisms – may explain why maternal care (or lack thereof) has a long-term effect on the behavior and hormone levels in mice.
To study the alleged causal relationship between the features of DNA methylation and changes associated with stress in the early stages of life, the authors analyzed DNA methylation profiles in mice that were weaned from their mother for three hours daily during the first ten days of life. Particular attention was paid to changes affecting the vasopressin gene (antidiuretic hormone, ADH), which regulates not only the introductory salt balance and blood pressure, but also affects mood and cognitive behavior. The vasopressin receptor is considered a promising therapeutic target for the treatment of stress-related diseases.
From the age of six weeks to the middle age (one year) in mice that experienced stress at the beginning of life and, as predicted, showed deviations from the norm in behavior and hormonal background, significantly reduced levels of DNA methylation (and, accordingly, more active gene expression) were recorded in the regulatory region of the vasopressin-coding Avp gene in brain cells. This hypomethylation was characteristic of the neurons of the hypothalamic paraventricular nucleus, a region of the brain involved in the regulation of the synthesis of stress–related hormones. Elevated levels of vasopressin informational RNA were also observed in the cells of such animals, which confirms an increase in hormone synthesis as a result of reduced DNA methylation.
In other words, the genome, as it were, remembers the stress suffered by the body at the beginning of life. These "memories" are recorded as lifelong changes in the methylation of certain genes in certain brain cells.
Further experiments showed that a decrease in the methylation of the Avp gene under the influence of early stress effects occurs as a result of a decrease (due to the opposite process – hypermethylation of the corresponding gene) in the synthesis of the MeCP2 protein involved in the primary activation of DNA methylating proteins.
According to Moshe Szyf, an epigeneticist from McGill University (Montreal, Canada), the concept that social status in the early stages of life can influence the state of health in adulthood is truly revolutionary. The results of the presented work materialize this theory, revealing in detail the underlying molecular mechanism of psychological and physiological phenomena.
Understanding the molecular details underlying the described phenomenon is necessary for the development of potential treatments for mental disorders, the roots of which lie in early negative experiences.
Spengler emphasizes that treatment of the consequences of early stress should be started as early as possible. A possible therapeutic approach is to restore the activity of MeCP2, however, unfortunately, it is impossible to eliminate DNA methylation due to the extreme stability of this chemical label. Therefore, the only possible approach to the treatment of stress-related conditions suffered in the early stages of life is to optimize the phenotype, for example, by blocking vasopressin receptors in people with elevated levels of this hormone.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of The Scientist: Early stress alters epigenome.
13.11.2009