Traumatic events leave their mark, for better and for worse.
Psychologists have long recognized that the negative effects of trauma experienced by parents can be seen in their children, but it’s not clear what molecular mechanisms drive the transmission.
A research team led by Isabelle Mansuy, professor of neuroepigenetics at the University of Zurich and ETH Zurich, has for the first time tested in mice the degree to which the beneficial—rather than the harmful—effects of stress can be passed to following generations.
The researchers subjected newborn male mice to traumatic stress by removing them from their mother at irregular and frequent intervals and also by severely stressing the mothers.
They then used tests to analyze the behavior of these pups later in life and the behavior of their offspring. They then compared them to control mice not subjected to stress.
The offspring of the stressed mice handled complex tasks more efficiently than the control group, experiments show.
Difficult situations
For example, one test revealed that the offspring of stressed fathers adapted better to changing rules on a task to earn a drink reward when they were thirsty. They reacted more flexibly.
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In another test, the mice had to poke their nose into a hole when prompted by a light signal but only after a pre-determined delay of 6, 12, or 18 seconds to get water. The stressed mice and their offspring performed the task better than the control mice at the long time interval of 18 seconds, which was especially challenging.
This result was interpreted by the researchers as evidence for improved goal-oriented behavior in difficult situations. Since the fathers were kept apart from their offspring and the mothers, the young animals cannot have learned this behavior. Rather, they must have inherited it via molecular pathways in germ cells.
“We are not in any way suggesting that early-childhood trauma is somehow positive,” says Mansuy. But she adds that her study on mice demonstrates how extreme stress can positively or negatively affect the brain and behavior across generations.
Altered gene
To determine how this behavior is expressed and transmitted to the next generation, the researchers examined the activity of a gene, a mineralocorticoid receptor gene previously implicated in flexible behavior.
Mansuy’s team discovered that epigenetic marks, which determine how much a gene is expressed, were altered on this gene, both in the brain and sperm of the stressed adult mice.
The altered marks were passed on to the next generation probably through the sperm, and may partly be responsible for the altered behavior. The mineralocorticoid receptor in question binds signal messengers such as the stress hormone cortisone, which initiates a signaling cascade in neurons.
“Our results show that environmental factors change behavior and that these changes can be passed on to the next generation,” explains Mansuy.
Future therapies?
This finding—that not only a parent’s susceptibility to psychological disorders can be passed on to its offspring, but also its improved goal-oriented behavior in difficult situations—might prove to be of value to clinicians. Doctors could help post-trauma patients suffering from depression to build on these sorts of strength.
The implication of the mineralocorticoid receptor gene also may be a good starting point for potential future medical therapies.
The study is published in the journal Nature Communications.
Source: ETH Zurich
