It’s possible that the impact of traumatic experiences may be epigenetically inherited via molecular memory that is passed down through generations. Although still controversial, new research takes this concept a step further and demonstrates that traumatic behavior could be reversed when it would otherwise be inherited. A study, published in Neuropsychopharmacology, was conducted by researchers at the University of Zurich and ETH Zurich and showed that behavioral symptoms associated with trauma in male mice and their offspring can be undone with environmental enrichment. Specifically, this reversal and removal of traumatic symptoms were found to be linked to the epigenetic regulation of the glucocorticoid receptor gene.
The likelihood of developing behavioral and psychiatric disorders later in life is thought to be increased by trauma. The detrimental effects of such an event can be seen in the children of those who were impacted by it, despite these children never having experienced it themselves. This inherited molecular memory can be detected in the child’s epigenome.
Lead author Katharina Gapp, along with a group of scientists, are thought to be the first to show that trauma-related behavioral alterations can be epigenetically reversed in male mice. These behavioral changes come about as a result of a traumatic event experienced by mice, in this case, being unpredictably separated from their mother several times. According to the researchers, these changes are “accompanied by increased glucocorticoid receptor (GR) expression and decreased DNA methylation of the GR promoter in the hippocampus” of the offspring of traumatized mice.
The hippocampus is essential for cognitive processes and plays an important role in the regulation of stress responses. The increased glucocorticoid receptor expression found in this area of the brain was due to epigenetic dysregulation of the gene for glucocorticoid receptors. These receptors are responsible for binding to stress hormones like cortisone.
DNA methylation is a well-known epigenetic mechanism that typically silences genes and is defined by the addition of a methyl group to particular locations on DNA. The trauma removed some of these DNA methylation marks, thereby bolstering the activity of the gene and increasing the amount of glucocorticoid receptors produced. Not only was this disruption observed in the hippocampus of the mice offspring, but the epigenetic changes were also found in the germ cells of the fathers of these mice, who were separated from their mothers early in life. The researchers believe that the changes in DNA methylation may be transmitted across generations through the sperm.
However, if the male mice experience trauma early in their lives and then later live in pleasant environmental conditions as they age, their behavior returns to normal and their offspring develop normally. This low-stress paternal environment enrichment and subsequent amelioration of traumatic behavior symptoms is “associated with the reversal of alterations in GR gene expression and DNA methylation in the hippocampus of the male offspring,” the researchers reported.
“Long after the traumatic experiences themselves, living in enriched conditions reverses the behavioral symptoms in adult animals and also prevents the transmission of these symptoms to the progeny,” concluded Isabelle Mansuy, Professor of Neuroepigenetics at the University of Zurich and ETH Zurich and co-author of the study.
The research team has demonstrated that the negative effect of trauma experienced as a child could be corrected by an enriched environment with low stress in adult life. At the same time, fixing the aberrant DNA methylation pattern prevents the behavioral symptoms from being passed on to the offspring.
Research continues to explore the ways in which life experiences may be passed on epigenetically through generations. This knowledge may even help lead to novel treatments or new approaches to therapy. “Until now, only pharmacological drugs were known to correct epigenetic alterations in a consequential way for behavior,” Mansuy said. “Now we know that this is also possible through environmental manipulations such as enriched conditions.”
Source: Gapp, K., Bohacek, J., Grossmann, J., Brunner, A.M., Manuella, F., Nanni, P., Mansuy, I.M. (2016). Potential of Environmental Enrichment to Prevent Transgenerational Effects of Paternal Trauma. Neuropsychopharmacology, advance online publication.
Reference: University of Zurich. Not only trauma but also the reversal of trauma is inherited. University of Zurich News. 22 Jun 2016. Web.