Can we inherit fear from our parents?
Offspring of traumatised mice show signs of the trauma for two generations. Researchers think the answer may be in their RNA. Yi-Di Ng reports.
Children inherit their father’s characteristics via his genes. Some animal studies suggest they can also inherit his experiences. But how? A team of researchers from the University of Zurich has made a big step towards finding that answer.
Early life trauma alters the expression of small molecules called microRNA in the sperm of mice, Isabelle Mansuy and her colleagues report in Nature Neuroscience.
“The study is fascinating,” says geneticist Catherine Suter at the Victor Chang Research Institute in Sydney. “There’s a big gap in our knowledge about how environmental stress causes the effects we see in the next generation.”
The researchers traumatised litters of newborn mice by randomly separating them from their mothers for three hours every day for two weeks. The unpredictable separation is extremely stressful for both the mother and the pups, says Mansuy. The traumatised mice appeared to mature normally. It was only when the researchers subjected them to behavioural tests that differences became apparent. The traumatised mice appeared to be reckless, wandering into bright, open spaces that mice usually avoid. Yet they also appeared to be depressed. When placed in a tank of water they gave up and floated instead of trying to swim to safety.
When males from the traumatised litters fathered offspring, their pups displayed similar abnormal behaviour even though they had never experienced trauma. The pups’ insulin and blood glucose levels were also lower than in normal mice – a symptom of early life stress. The offspring seemed to have inherited the effects of their fathers’ trauma. Furthermore, the next generation, that is the grandchildren of the original stressed mice, also showed abnormal behaviours. How could trauma be transmitted down the generations?
The pups that developed from these embryos displayed the same
behavioural and metabolic abnormalities as the traumatised fathers.
The researchers analysed the traumatised fathers' brain tissue, specifically in a region called the hippocampus, where memories are formed. They noticed larger than normal quantities of tiny RNA molecules called microRNA. Like tiny switches, these molecules are known to turn the activity of genes on or off.
An abundance of this microRNA was also detected in the traumatised fathers' sperm and in the brain tissue of their offspring. Could it be that the microRNA was somehow imprinted with the experience of the trauma, transmitting the memory to the offspring? To answer this, the researchers extracted the microRNA from the sperm of traumatised mice and injected it into embryos. The pups that developed from these embryos displayed the same behavioural and metabolic abnormalities as the traumatised fathers, while pups injected with RNA from un-traumatised fathers did not. It was strong support for the hypothesis that the sperm RNA was transmitting the experience of trauma.
The challenge now was to figure out how the microRNA could alter behaviour and metabolism in the offspring. First, the researchers managed to identify one of the overabundant microRNA molecules, called miR-375.
MiR-375 is known to tone down the production of a protein called β-catenin, which is involved in some types of metabolic stress. Indeed the offspring had slightly less β-catenin in their brains than unstressed mice. But as far as explaining the inherited effects, Mansuy is quick to warn, “it’s not responsible for everything”.
There are still many unanswered questions. How does trauma change microRNA levels in the brain? And how does that microRNA then end up in sperm? Furthermore, as Suter points out, the offspring of the traumatised mice did not carry unusual microRNA in their sperm, yet still passed abnormal behaviour to their pups.
“RNA may be implicated,” says Suter, “but I think a lot more work needs to be done.”