There is growing evidence that inheriting stress responses from parents and grandparents is common and can lead to both physiological and behavioral changes. Gapp and colleagues identified the mechanism that results in this inherited stress response and found a way to reverse these effects.
Recent research has shown that early life stresses can have lasting effects on physiology and behavior, affecting everything from how social we are to our risk for certain diseases, like hypertension. In some cases, these effects can be beneficial, resulting in increased resilience. These responses can then be passed on to the next generation, so inheriting stress can contribute to cross-generational health outcomes. However, these behavioral and physiological responses can also be modified by our experiences later in life, which suggests that the effects of these stresses can be altered.
These physiological and behavioral responses are likely mediated by the hypothalamic-pituitary-adrenal (HPA) axis and, in particular, the glucocorticoid receptor (GR). The HPA axis is a set of interactions and feedback loops between the hypothalamus (a region of the brain), the pituitary gland (a gland that sits just below they hypothalamus), and the adrenal glands. This axis regulates the stress response, as well as many body processes including immune responses. The GR serves as a receptor for cortisol, a stress hormone, in many tissues throughout the body.
In a report published in the journal Neuropsychopharmacology, Gapp and colleagues used mice to investigate the relationship of the HPA axis and early life stresses in modifying physiology and behavior across generations. Each experimental or control group included 20 to 30 females and their litters. For the experimental group, researchers separated newborn pups from their mothers at unpredictable intervals for periods of three hours. These stressed mice formed the first generation. A subset of both control mice and those who were subjected to early life stress were placed into enriched environments, which included social groups in cages with multiple levels and a maze. As adults, these first-generation mice and their offspring were tested for their response to unpleasant or stressful conditions, including exposure to a brightly lit box with access to a darkened escape room, and a series of electric shocks to the feet that could be alleviated by poking their noses into a hole. The researchers also determined what genes were being expressed in the hippocampus throughout the experiment using a technique called Real-Time PCR, and analyzed the brains of the mice for protein expression.
Gapp and colleagues found that second-generation mice whose parents had experienced stressful conditions were less likely to escape adverse conditions than control mice, and more likely to actively resist those conditions. This suggests that these second-generation mice inherited the stress-induced behavioral responses of their parents, which include better coping and greater behavioral flexibility. Furthermore, first-generation mice that had been stressed as newborns but were reared in enriched environments responded to stress in the same way as control mice, and so did their second-generation offspring. This result suggests that enriched environments can undo the inherited stress response, and opens up the possibility of targeted diagnostic and therapeutic approaches for individuals who have experienced trauma.
Additionally, Gapp and colleagues found that these behavioral responses were paralleled by GR expression in the hippocampus, and this expression was mediated by chemical modifications of DNA called methylation. These chemical modifications can be inherited, providing a mechanism for the passing of these stress responses across generations.
Written By: C. I. Villamil