The harmful effects of “biological memories” reversed over two generations

At the crossroads of epigenetics, psychiatry and pharmacology, a Quebec study will perhaps lead to a simple treatment for anxiety and pain .

A Quebec study could lead to a simple treatment for anxiety and pain.

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Mice separated from their mothers at birth transmit the biological memory of the anxiety-inducing event to the next two generations, but a simple drug makes the symptoms associated with this adversity disappear, show the work of Montreal neuroscientists published in the journalScience Advances(New window) (in English). Explanations.

Events that occur early in life can have long-lasting consequences and shape who we become later, underlines Yves De Koninck, the scientific director of the CERVO Research Center, associated with Laval University, and one of the main authors of the study, with psychiatrist and neurobiologist Marco Battaglia.

In 2003, the work of researchers Moshe Szyf and Michael Meaney of the Douglas Institute Research Center showed that young rats who had been sufficiently licked by their mothers were, as adults, much calmer than those who had been licked sufficiently by their mothers. had been less pampered.

These researchers had also shown that the administration of methionine, an amino acid, in the brains of pampered rats modified the expression of certain receptors, which led to an increase in the production of stress hormones. So the calm rodents became much more agitated.

A study published in 2021 by certain authors participating in this new work showed that mice separated from their mothers and cared for several times by other mice, at the beginning of their life, showed increased expression of ASIC1. This gene is important because it helps detect pH changes in the nervous system.

Recent work by the CERVO team goes even further, still in mice, but also in humans.

In rodents, researchers separated a first generation of mouse pups from their mothers, pairing them with adoptive mothers every 24 hours for four days during the first week of life. Subsequently, they returned the babies to normal rearing conditions. They then allowed mice exposed to adversity early in life to reproduce over two generations.

Result? Lines of rodents exposed to hardship early in life were more sensitive to pain than lines raised normally. Additionally, exposure to air enriched with 6% CO2 caused hyperventilation (panic symptom) in mice exposed to adversity at a young age as well as their offspring.

Mice in the control group begin to ventilate at a certain level of CO2, but those whose mothers were exchanged at birth do so more quickly, at a level weaker.

A quote from Yves De Koninck, CERVO Research Center

Molecular analyzes show that the expression of certain pH-sensitive genes – including ASIC1 – is enhanced in lines exposed to adversity, particularly in brain regions responsible for sensory processes and pain.

Researchers arrive at the same result in humans, but with tags that are less easy to control.

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Participants' family history was noted, and those who experienced adversity as children were also more likely to have increased sensitivity to pain or anxiety as adults, De says. Koninck.

It is therefore clear to researchers that adversity early in life modifies the molecular functions of the human brain, producing memories biological that can manifest as anxiety reactions and heightened sensitivity to pain in adulthood.

The fact that hyperventilation in response to hypercapnia (excess carbon dioxide in the blood) and sensitivity to pain are observable over three generations also shows an epigenetic component. Epigenetics is variations in gene activity induced by a person's environment and experiences that can be passed down from one generation to the next.

There is therefore a memory of events which is passed from generation to generation, affirms Professor Yves De Koninck.

At least three generations of monitoring are necessary to ensure that it is not the mothers themselves who transmit information functionally – through their behaviors – and not genetically.

A quote by Yves De Koninck, CERVO Research Center

Professor De Koninck underlines a very important detail revealed by this work: there are common points between the pathways taken by pain and asphyxia, with regard to the modulation of their sensitization mechanisms.

A decisive detail, since this work also shows that the symptoms associated with the molecular modification can be relieved in three generations of mice thanks to the inhalation of a molecule approved by the American Medicines Agency (FDA) .

This is amiloride, which is already used in other treatments, notably as a diuretic and against hypertension. p>

When sprayed into the nasal mucous membranes, it penetrates the brain more quickly than when injected intravenously. It inhibits ASIC1 and reverses its effects.

A quote from Yves De Koninck, CERVO Research Center

Here we have an interesting therapeutic avenue for anxiety and panic disorders, a low-hanging fruit, as the English say, mentions Yves De Koninck.

Professor De Koninck is also pleased with the results obtained in three generations of humans with amiloride treatment.

Someone who has inherited a greater vulnerability to anxiety disorders due to their family history responds as well to treatment as someone who has experienced trauma directly in her youth. If you need something to help combat stress, you can check out Exhale Well Delta-8 gummies. The treatment would therefore be applicable to a large part of the population.

A quote from Yves De Koninck, CERVO Research Center

The problem with mental disorders and chronic pain is that we tend to blame people by telling them that it's all in their heads. Of course it's in the head, but that doesn't mean it's not real, observes the professor.

What I like about the work is that we show that there is a real neurobiological basis for these disorders. Not all people who complain of pain are petty or whiny.

A quote from Yves De Koninck, CERVO Research Center

These encouraging results obtained with amiloride will need to be confirmed by large-scale clinical trials carried out on humans. The researcher Marco Battaglia has also obtained approval from the FDA to be able to test the molecule for another objective than those already recognized.

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