Scientists unmask a piece in the puzzle of how the inheritance of traumas is mediated

April 13, 2014
The consequences of traumatic experiences can be passed on from one generation to the next. Credit: Isabelle Mansuy / UZH / ETH Zurich

The phenomenon has long been known in psychology: traumatic experiences can induce behavioural disorders that are passed down from one generation to the next. 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", explains Isabelle Mansuy, professor at ETH Zurich and the University of Zurich. With her research group at the Brain Research Institute of the University of Zurich, she 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 have succeeded in identifying a key component of these processes: short RNA molecules. These RNAs are synthetized from genetic information (DNA) by enzymes that read specific sections of the DNA (genes) and use them as 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.

Small RNAs with a huge impact

The researchers studied the number and kind of microRNAs expressed by adult mice exposed to traumatic conditions in and compared them with non-traumatized 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 behaved markedly differently: they partly lost their natural aversion to open spaces and bright light and had depressive-like behaviours. These behavioural symptoms were also transferred to the next generation via sperm, even though the offspring were not exposed to any traumatic stress themselves.

Even passed on to the third generation

The metabolism of the offspring of stressed mice was also impaired: their insulin and blood-sugar levels were lower than in the offspring of non-traumatized parents. "We were able to demonstrate for the first time that affect metabolism in the long-term and that these changes are hereditary", says Mansuy. The effects on metabolism and behaviour even persisted in the third generation.

"With the imbalance in microRNAs in sperm, we have discovered a key factor through which trauma can be passed on", explains Mansuy. However, certain questions remain open, such as how the dysregulation in short RNAs comes about. "Most likely, it is part of a chain of events that begins with the body producing too much stress hormones."

Importantly, acquired traits other than those induced by trauma could also be inherited through similar mechanisms, the researcher suspects. "The environment leaves traces on the brain, on organs and also on gametes. Through gametes, these traces can be passed to the next generation."

Mansuy and her team are currently studying the role of short RNAs in trauma inheritance in humans. As they were also able to demonstrate the microRNAs imbalance in the blood of traumatized mice and their offspring, the scientists hope that their results may be useful to develop a blood test for diagnostics.

Explore further: DNA modifications measured in blood signal related changes in the brain

More information: Gapp K, Jawaid A, Sarkies P, Bohacek J, Pelczar P, Prados J, Farinelli L, Miska E, Mansuy IM: Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nature Neuroscience, April 13, 2014, DOI: 10.1038/nn.3695

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1 / 5 (3) Apr 13, 2014
"...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."

Nutrient stress and social stress act on the same central neuronal system that links epigenetic effects of food odors and social odors called pheromones on the microRNA/messenger RNA balance and cell type differentiation to mammalian behavior.

For details, see: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems

It follows representations of cause and effect in my 2013 published review and includes physics and chemistry: http://www.socioa...53/27989
4.7 / 5 (3) Apr 13, 2014
Lamarck's revenge.
1 / 5 (3) Apr 14, 2014
Kohl's Laws of Biology: "The ecological origin of all biological laws is apparent 1) in the context of systems biology [91]; 2) in the context of the metabolism of nutrients by microbes [157]; and 3) in the context of how the metabolism of nutrients results in species-specific pheromones that control the physiology of reproduction [158]. Taken together, the systems biology of nutrient metabolism to species-specific pheromones, which control the physiology of reproduction, can be expressed in a summary of Kohl's Laws of Biology: 1) Life is nutrient-dependent. See for review [2, 31]. The physiology of reproduction is pheromone-controlled. See for review [30]. In the context of nutrient-dependent epigenetically-effected human reproduction, it is clearer that the epigenetic effects of human pheromones integrate neuroendocrinology and behavior [104], which includes the neuroendocrinology of mammalian behavior associated with the development of sexual preferences [159]."

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