Jean Mary Zarate: 00:04
Hello, and welcome to Tales From the Synapse, a podcast brought to you by Nature Careers in partnership with Nature Neuroscience. I'm Jean Mary Zarate, a senior editor at the journal Nature Neuroscience.
And in this series, we speak to brain scientists all over the world about their life, their research, their collaborations, and the impact of their work. In episode 11, we meet a researcher who was set on understanding trauma and to what extent it passes from generation to generation.
Isabelle Mansuy: 00:40
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.
Isabelle Mansuy: 02:42
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.
Isabelle Mansuy: 05:00
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.
Isabelle Mansuy: 07:28
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.
Isabelle Mansuy: 09:35
Traumatic experiences can affect many people in the population. We naturally think of war conflict, but in the daily life in families, there are many different types of trauma.
Trauma can be physical violence, sexual violence, abuse, neglect, humiliation, verbal violence. Many things which can happen not only in low socioeconomic milieu but also in, in wealthy families, when you have abusive parents, abusive father, very often, or at work or at school.
I mean, the past couple of years around the globe, I mean, there have been a number of examples of abuse in children, whether in church, whether, you know, abusing in young women, in young girls.
So, we are concerned, I mean, this is a type of trauma, which is in the society everywhere, and can affect everyone. Of course, there is also people who are experiencing or exposed to very violent events, like war conflicts. If there are soldiers or even in countries which are going through, through major, major conflicts. It could be an accident, it could be a natural disaster.
You know, if, if there is a tsunami, for instance, in, in various countries, in the past two decades, I mean, that can be extremely traumatic for many people, and for a very long time.
Isabelle Mansuy: 11:24
Traumatic experiences can have multiple effects on the brain. It really depends on the severity of the trauma and on the age during which the trauma was experienced, and the duration of trauma.
If it’s a chronic trauma in childhood, you know, when the child brain is developing, it can have massive effects, not just effects in the cells, but also structural effects, and prevents the brain from developing normally from establishing proper connections.
If it’s a traumatic, one single traumatic event in an adult, it may have shorter lasting effects, which may be alteration of functions of some cells, and consequences of the the release of stress hormone in the body.
And there are different ways to measure the internal effects of trauma in the body. But it’s a bit complicated, because you imagine an engine, which is working more or less well, and starts to not work very well.
What is your readout, you cannot, you don’t really understand necessarily how the engine works. But you may look at the exhaust pipe and the gas, analyze the gas, and then realize that something is wrong.
So with the body, it’s a little bit the same. I mean, we don’t understand exactly how the body functions, but we have blood as a readout. We can take blood to analysis, like, look at the composition of blood and maybe guess that something is going wrong in the body and perhaps in the brain. But today, we don’t know exactly, we have only a very rough idea of what can be altered in the body due to traumatic experiences.
A child may have lots of difficulties in developing normally and being self confident, having self esteem and having a balanced behaviour. In adult it can modify behaviour, and people who have been, who have gone through an extreme stress, they may (or trauma), they may then be very fearful. They may have PTSD, which is an overreaction, or obsessive fear, which are not related to the environment. Someone can become suddenly very stressed and have the heartbeat, which raises, and starting to sweat and feel bad when there is no threat around.
Obsessive memories and traumatic memories can also happen in someone who has been experiencing traumatic experiences in traumatic events in childhood. So there can be multiple effects affecting the brain and the body.
Isabelle Mansuy: 14:44
It’s very important to understand biology, to understand how the brain functions, how the brain reacts to various environments, and to understand disease aetiology.
Why are people exposed to traumatic experiences, suffering all their life and why sometimes even the children suffer? We need to understand what are the origins of such disease and why someone gets a neuro, Alzheimer’s Disease, or a neurodegenerative disorder, or mood disorder. So this fundamental research is absolutely essential, to hope to obtain answers to these questions.
Isabelle Mansuy: 15:35
Yes, well, being a scientist is a very tough profession.
It’s very difficult to be to become a researcher and have the freedom to do the research you want.
But once you reach this level, it’s an extremely exciting, very interesting, very stimulating profession. Each day is different. And we have the freedom to work on things that we like. And you know, to discover how nature functions, how new things which have, which are not well understood, is extremely exciting.
And if on top of this, you’re working on something that can help medicine, to crack a problem, to work on a problem, which affects people in the society is makes the job even more interesting, more challenging. But really everyday, it fuels our everyday work. Curiosity and excitement by things which look mysterious, and also with the drive of changing, Doing something that can improve people that can be helpful for the society, for medicine. And for, yeah, for people in general. Being useful, being useful to research by bringing new knowledge and by discovering how the brain functions.
Jean Mary Zarate: 17:30
Now that’s it for this episode of Tales From the Synapse. I’m Jean Mary Zarate, a senior editor at Nature Neuroscience. The producer was Don Byrne. Thanks again to Professor Isabelle Mansuy, and thank you for listening