Isabelle Mansuy’s neuroepigenetics lab researches the impact of life experiences and environmental factors on mental health, exploring if these impacts can be passed on to descendants.
Epigenetic inheritance, she says, is not confined to diets and exposure of factors such as like endocrine disruptors or environmental pollutants. All of these can modify our body and have effects in our offspring. But Mansuy, who is based at the University of Zurich and Swiss Federal Institute of Technology in Zurich, Switzerland, also asks if trauma modifies not only our brains, but also our reproductive systems.
There is still a lot of work needed, she adds, but the possibility that depression or borderline personality disorder might be something inherited from parents would be important for patients and clinicians to understand.
Mansuy’s lab seeks to expose animals prenatally or after birth to conditions which mimic human stress. Her collaborators also provide access to blood and saliva samples from people exposed to childhood trauma, and medical students who are undergoing work placements in emergency rooms.
Excerpts from the transcript of the conversation between host Jean Mary Zarate and Neuroepigenetics researcher Isabell Mansuy – listen to the full episode at Nature.com
Isabell Mansuy:
I’m Isabelle Mansuy. And I'm professor in neuroepigenetics at the University of Zurich, and the Swiss Federal Institute of Technology in Zurich, Switzerland.
Neuroepigenetics is a new discipline in biology and neuroscience, which combines neuroscience and epigenetics.
So it’s a discipline which studies the intimate mechanisms which regulate brain function, so the functions of the nervous system.
So classically, we know that the genome, and genes that it contains, or it carries, regulate complex functions. Now, with epigenetics, we are looking at factors and mechanics which are beyond the genetic sequence itself, beyond the DNA sequence, beyond the genome, which regulate the function of the genome.
So neuroepigenetics, it’s really looking at the heart of brain cells or nervous, cells of the nervous system, looking in the nucleus at the level of the genome, to understand how the genome is regulated, and what are the consequences for behaviour and for brain functions.
Not only it’s how the brain develops, how the brain functions, how the brain can drive our thoughts, how the brain can drive our movements, how all of this is regulated, and how diseases can affect the nervous system, mental health and physical health because you have, if you have a neurodegenerative disease, your body is going to be affected, and your internal organs.
So it’s really the general science of understanding how brain cells, or cells of the nervous system, function.
My work is in a discipline which is even different, or which complements neuroepigenetics, which is epigenetic inheritance.
The overall question is how indeed life experiences or environmental factors can shape, augment our brain and our body and our mental health. Not just ours, but also the one from our children, our descendants.
So there are multiple questions here. First is how our life experiences can modify our brain, but also our reproductive system, our germ cells. So in men, sperm cells, and in women, all sides.
And if these reproductive cells are modified by the life experience, or traumatic experiences, for instance, at the same time as the rest of the body, this could be responsible for the transfer, the transmission, of some of the effects of the exposure to the children.
This derives from observation, epidemiological studies in human that for many psychiatric disorders, borderline personality disorder, anxiety, depression, very severe and complex diseases.
In many cases, people have been exposed to traumatic experiences in childhood. Not necessarily them, but sometimes the parents or grandparents.
So the idea emerged that such type of adverse extreme experiences in childhood can modify the body so much that it can have imprints or traces even in reproductive cells.
And these traces may be responsible for the expression, the manifestation of symptoms of exposure in the children, or perhaps even the grandchildren.
So what we are interested in is identifying these molecular traces in germ cells. And for this, we are using animal models.
Animal models are used really to dissect out the mechanism, but all of this initially was observed in human.
There have been many cohorts linked to war trauma, linked to different experiences that populations, oppressed populations, for instance, have been, have gone through.
In animal research, we are trying to mimic human conditions by exposing the animals, either prenatally or after birth, during development or in adulthood, to various conditions which mimic, which try to mimic the best human stress.
Like mouse, we can use restraint, for instance, Or during development, we can use maternal separation unpredictable maternal separation.
And by using these paradigms, which can vary in severity and duration in chronicity, we can induce stress, signs of stress in the animals, and then benefit from that, or explore these animals to study the makeup, the underlying mechanism across tissues.
We had a cohort of traumatized children at some point in Pakistan. But it was, it’s a small cohort that we put together to collect blood as a pilot or proof of principle of some of the results we have collected in mice. Other than this, we are not directly involved with patients.
We have collaborations with the psychologist, psychiatrist through different consortia. I belong to four different consortia, three European and one Swiss, where I have access to blood or saliva if I want, with different people, people exposed to childhood trauma or to, we have a cohort of medical students who are in the emergency room and who go through several weeks of very stressful life.
So these type of of studies, and we can have access to the biological fluids from these people and do analysis if we want. But ourselves, we are not directly involved in these patients.
And indeed, there are two levels, I think. First of all is the knowledge, the gaining knowledge because epigenetic inheritance itself, it's a form of heredity, which is linked not only to life experiences, but also to diets, to exposure of various factors like endocrine disruptors, or pollutants in the environment. It is known that all these factors, elements, the things that we encounter during our life, can modify our body and have effects in our offspring.
So the general concept of epigenetic, of inheritance, this form of transmission of acquired traits. There are features that an organism starts developing after being exposed to some factor, and that these features are passed to the following generations. And that is not by culture, by behaviour or by anything else, but embedded into reproductive cells.
So when this relates to traumatic experiences, or childhood adverse experiences, our finding, or the results of our research, could help people who are affected by this in their mental health, in their physical health.
There is still a lot of work needed to be able to help these people directly. But if we could already confirm the possibility, that indeed, complex diseases like depression or borderline personality disorder, may not necessarily be caused by something the person has done wrong, but could be something that is inherited from mum or dad.
That would already be something very important for people to know and for psychiatrists and for medicine in general.
Listen to the full conversation (17:00) at Nature.com
