Hereditary trauma demonstrated in mice

Researchers from the University of Zurich and ETH Zurich have discovered a piece in the puzzle which explains how the inheritance of traumas may be mediated. Psychologists have long known that traumatic experiences can induce behavioural disorders that are passed down from one generation to the next, but it is only recently that scientists have begun to understand the physiological processes underlying hereditary trauma.

“There are diseases such as bipolar disorder that run in families but can’t be traced back to a particular gene,” explained Isabelle Mansuy, a professor at ETH Zurich and the University of Zurich, who has been studying the molecular processes involved in non-genetic inheritance of behavioural symptoms induced by traumatic experiences in early life.

Mansuy and her team at the university’s Brain Research Institute have now succeeded in identifying a key component of these processes: short RNA molecules. These RNAs are synthetised from DNA by enzymes that read genes and use them as a template to produce corresponding RNAs. Other enzymes then trim these RNAs into mature forms. Cells naturally contain a large number of different short RNA molecules called microRNAs. They have regulatory functions, such as controlling how many copies of a particular protein are made.

The researchers studied the number and kind of microRNAs expressed by adult mice exposed to traumatic conditions in early life and compared them with non-traumatised mice. They discovered that traumatic stress alters the amount of several microRNAs in the blood, brain and sperm - while some microRNAs were produced in excess, others were lower than in the corresponding tissues or cells of control animals. These alterations resulted in misregulation of cellular processes normally controlled by these microRNAs.

After traumatic experiences, the mice partly lost their natural aversion to open spaces and bright light and had depressive-like behaviours. These behavioural symptoms were transferred to the next generation via sperm, even though the offspring were not exposed to any traumatic stress themselves.

The metabolism of the offspring was also impaired: their insulin and blood-sugar levels were lower than in the offspring of non-traumatised parents. Furthermore, the effects on metabolism and behaviour persisted in the third generation.

“We were able to demonstrate for the first time that traumatic experiences affect metabolism in the long term and that these changes are hereditary,” said Mansuy.

“With the imbalance in microRNAs in sperm, we have discovered a key factor through which trauma can be passed on,” she added, though it is still unknown how the dysregulation in short RNAs comes about.

Mansuy and her team are currently studying the role of short RNAs in trauma inheritance in humans, and hope their results in mice may be useful in developing a blood test for diagnostics. They also suggest that acquired traits other than those induced by trauma could also be inherited through similar mechanisms.

Their results have been published in the journal Nature Neuroscience