Mice ‘warn’ sons of dangers through inherited fears

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It seems that inheritance is not simply about parents passing genes to their offspring. Some inheritable changes in gene activity can be passed on without changing the DNA sequencing, as researchers from Emory University School of Medicine claim that mice can inherit the memory of their ancestor’s traumas and display similar responses when faced with the stimuli.

The findings of this latest study in epigenetics, published in Nature Neuroscience, show that the offspring of laboratory mice trained to fear a particular smell demonstrated the same fear reaction as their ancestor.

They were also able to detect smaller concentrations of the odor than the offspring of untrained mice.

Co-author of the study, Brian Dias, explains the importance of the findings:

“Knowing how ancestral experiences influence descendant generations will allow us to understand more about the development of neuropsychiatric disorders that have a transgenerational basis.”

For the experiments, mice were subjected to small electric shocks while in a chamber smelling of acetophenone, a chemical that smells like cherry blossom. The mice soon associated the smell with pain, quivering when just the smell was present.

Learning to be scared

Mice that were taught to fear the smell of acetophenone had an altered pattern of methylation – a chemical modification of DNA that fine-tunes gene behavior – on the odor receptor gene M71.

Despite not even having been conceived when their ancestors undertook fear training, the offspring reacted with fear when they smelled the acetophenone.

Kerry Ressler, co-author of the study, explains that the offspring responded strongly to far smaller amounts of the odor.

The researchers claim that the young mice did not respond in the same way to other smells, and when compared with the offspring of untrained mice, their reaction to just a whiff of acetophenone was about “200% stronger.”

The scientists then examined the gene M71, which controls the functioning of the odor receptor in the nose that responds to the cherry blossom smell.

They found that the gene’s DNA coding had not changed but it did carry epigenetic marks that changed its behavior and caused it to be “expressed more” in the offspring.

This alteration also caused a physical change in the descendant mice’s brains – they all had a larger glomerulus – a section in the olfactory bulb.

The scientists did discover that DNA from the sperm of smell-sensitized father mice had changed. They claim this is an example of an “epigenetic” alteration: transmitted not in the letter-by-letter sequence of the DNA, but in its packaging or chemical modifications.

Interestingly, the scientists found that the sons of the trained mice carried the altered gene expression in their sperm and transmitted it to their own offspring.

The results of this study are “encouraging,” according to Wolf Reik, head of epigenetics at the Babraham Institute, Cambridge, UK, pointing out that while they suggest transgenerational inheritance does exist, more research is needed before it can extrapolated to humans.

But Ressler is hopeful:

“Such interventions could form the core of a treatment to prevent the development of neuropsychiatric disorders with roots in ancestral trauma.”