The University of Haifa researchers, Dr. Inna Gaisler-Salomon and doctoral student Hiba Zaidan, in collaboration with Prof. Micah Leshem, found in previous studies that exposing rats to stress during adolescence, before they ever become pregnant, causes behavioral changes among their direct offspring when the latter reach adulthood. The researchers also found a gene (CRF1) related to stress which expresses itself differently in the brain of individual offspring from the moment they are born. According to the researchers, this finding suggests that it is not maternal care which influences variations in offspring, regarding stress.
In the current study, Dr. Gaisler-Salomon and a doctoral student in her lab (Ms. Zaidan) examined whether the effects of exposure of a female rat to stress before pregnancy affects not only her children but also her grandchildren. In addition to the CRF1 gene they tested for the presence of the hormone Corticosterone – a stress hormone that corresponds to Cortisol in humans and is released in response to stress . As in previous studies, the researchers exposed the female rats, when still adolescents, to minor stress involving changes in temperature and routine for a week. Their direct offspring grew up without any stress-inducing intervention, as did their grandchildren. The third generation of rats (the grandchildren) underwent different tests that measure anxiety-like behavior and the acquisition of fear. In addition, for the second and third generation offspring the levels of the CRF1 expression in the brain as well as the levels of Corticosterone were also measured.
The findings indicate that the effects of stress on the first-generation mother rat continue to influence her grandchildren on all three levels: behavioral, hormonal, and the manifestation of the CFR1 gene. On the behavioral level, the third generation descendants (mainly females) were, perhaps surprisingly, more “daring,” spent more time in the “frightening” parts of the maze, and exhibited less anxious behavior in various tests when compared with the offspring of rats that were not exposed to stress. In addition, the offspring (both male and female) of the rats exposed to stress demonstrated a more rapid acquisition of fear relative to the descendants of the control group.
“It’s possible to try and explain the results as showing that the rats whose grandmother was exposed to stress displayed more adaptive behavior to their surroundings. Wherever greater curiosity was needed to improve their chances of survival, they displayed curiosity, but the moment they were exposed to a frightening event, they learned quickly and reacted more extremely to this event. In any case, it is clearly impossible to talk in a dichotomous fashion about the positive or negative impact of the stress their grandmother was exposed to. This is a complex effect that depends on the context of the situation,” said the researchers. They also found that behavioral differences among the first generation of rats which were exposed to trauma were different from those found among the second generation. In other words, the effect of the trauma is transmitted between generations, but it affects each generation differently.
Both on the genetic and hormonal levels similarities and differences were found between the generations. The CRF1 gene which expressed itself strongly among the first generation was manifested at too low a level in the second generation when compared with the control groups. However, the Corticosterone hormone was found in higher levels among both the first and second generations.
“Adolescence is a very sensitive period, and our studies show that exposure to stress at this stage of life affects not only the affected female, but also the behavior and stress hormone levels of her first and second-generation offspring. Similar studies have been done, but most of them explore the consequences of stress to male, not females. Our studies further suggest that there are processes unrelated to maternal care that can explain how information is transmitted from generation to generation. The exciting new field of epigenetics can explain some of the findings,” concluded Dr. Gaisler-Salomon.
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