December 1, 2013

expert reaction to new research into epigenetic transfer of experience in mice

Nature Neuroscience published research demonstrating that mice biologically inherit information learned by their grandfathers by training mice to fear a cherry blossom-like smell and then allowing them to mate.

Prof Wolf Reik, Head of the Epigenetics and Chromatin Programme, Babraham Institute, said:

“Transgenerational epigenetic inheritance is an exciting area of modern biology, where this type of inheritance seems common in plants, but perhaps not so common in animals. This may be because animals have a powerful system of ‘erasing’ epigenetic marks in germ cells (eggs and sperm). Nevertheless, more recent studies have shown that this ‘erasure’ is not fail-safe, and that there is therefore the potential for epigenetic information to be passed down the generations. The paper by Dias and Ressler shows that adult mouse males subjected to odor fear conditioning had offspring that inherited an altered response to the odor, together with altered expression of the specific receptor for the odor. Interestingly, sperm DNA had a different epigenetic pattern (DNA methylation) in this specific receptor gene, suggesting that this could form the basis for the transgenerational inheritance. These types of results are encouraging as they suggest that transgenerational inheritance exists and is mediated by epigenetics, but more careful mechanistic study of animal models is needed before extrapolating such findings to humans.”

Prof Marcus Pembrey, Emeritus Professor of Paediatric Genetics, University College London, said:

“The Dias and Ressler paper on fear-conditioning in mice with the specific odour (Acetophenone) is important for two reasons. It addresses constitutional fearfulness that is highly relevant to phobias, anxiety and post-traumatic stress disorders, plus the controversial subject of transmission of the ‘memory’ of ancestral experience (literally shocking in this case) down the generations. It provides compelling evidence of biological transmission of such a ‘memory’, together with associated brain changes, from shocked adult male mice (F0) to their sons (F1) and then grandsons (F2). The experiments incorporated another specific odour (propanol) as a control, and were carefully designed to rule out confounding by social, learning and imitation transmission across the generations.

“Interestingly they expose adult male mice and still get clear transgenerational responses. Many previous experiments have exposed the rodent in early life e.g. in utero via the pregnant mother or in the neonatal period, because of evidence that early development is an exposure sensitive period for epigenetic alterations such as DNA methylation, which may or may not be directly passed on in sperm. The specificity of the odour Acetophenone is linked to a specific odour receptor Olfr 151, allowing a relevant analysis of the associated brain structural changes with conditioning; which amazingly the F1 and F2 also have. The above specificity also allows them to look at the right place in sperm DNA for methylation changes, namely the Olfr 151 gene, which they find.

“Pavlov did a somewhat similar ‘conditioning’ mouse experiment 90 years ago¹, based on food not fear, and reported that successive generations took fewer and fewer training sessions before they would search for food on hearing a bell even when food was absent. But such ideas of biological inheritance of experience fell out of favour during the 20th century.  If alive today, Pavlov would have been delighted by the Dias and Ressler paper, first as a vindication of his own experiment and results, and second by the amazing experimental tools available to the modern scientist. It is high time public health researchers took human transgenerational responses seriously. I suspect we will not understand the rise in neuropsychiatric disorders or obesity, diabetes and metabolic disruptions generally without taking a multigenerational approach.”

¹Quoted in: CL Morgan in ‘Evolution in the light of modern knowledge’ 1925 Blackie and Son Ltd, London. pp 143

‘Parental olfactory experience influences behavior and neural structure in subsequent generations’ by Dias & Ressler  published in Nature Neuroscience on Sunday 1 December.