Mexico: Researching the Brain Plasticity and Breaking the Stigma of Mental Illness

He has a passion for understanding that, what makes us human. It all started with observing neurons in a microscope, just like a Nobel Laureate 100 years ago. And this Mexican neuroscientist also wants to raise awareness of mental health to prevent the so common social stigma. Depression is one of the most common mental illnesses in the world’s population and one of the biggest risk factors for depression is chronic stress. Also, an illness that has gotten the attention of the 32 year old researcher Hiram Tendilla Beltran from Puebla, Mexico. His special interest is the plasticity of the brain.

What makes us human – Brain plasticity and mental illnesses     
Hiram’s eyes glow with fascination, when he tries to explain what’s all this with brain plasticity about: “All our cells, that are these basic units that compose us have to adapt both functionally and structurally so this phenomenon in general of our cells is known as plasticity. How do they adapt? A cell can function in a specific way and with few nutrients, it adapts. But it can also be in a structural way. Maybe it needs to be closer to the neighboring cell, so it generates projections that allow it to be closer to the neighboring cell, or this second neighbor is having a process that is causing some discomfort. So, it moves away from this neighboring cell. So, this is both functional and structural adaptation specifically in the brain, known as neuroplasticity because it is the neurons that adapt. So, this plasticity is fundamental for the development of our brain. We have to generate connections known as synapses to form neural networks that are the functional substrate of the brain. So, in this way these neural networks are formed partly by plasticity. Once we have our brain fully developed, it allows us, for example, to perceive reality adequately. I am in an environment where I feel safe. I am in an environment in which I know that maybe I can consume food in a safe way and then that allows the species to survive and develop”.

And plasticity has to do with development of mental illnesses, Hiram explains: “This plasticity depends on many factors and so there are factors that can alter it. So, if plasticity is altered it can alter the development of the brain. So consequently, there will be people who are not adequately interpreting reality, who then see as aversive or harmful a stimulus that is not, and this is when neurodevelopmental disorders arise, such as autism spectrum disorders, schizophrenia. Those are people who cannot adequately perceive their reality, so they do not have a response that is congruent to the stimulus that is being presented to them. So, this is where many alterations arise, symptoms of these illnesses, where this illness arose from, this incapacity of the brain to be able to adapt adequately.”

He makes another example with the so common mental condition, stress: “When stress is chronic, it compromises brain plasticity and thus compromises these neural networks and also makes us unable to perceive reality adequately. That leads us to these episodes of sadness, lack of anhedonia, lack of pleasure, and also generates this mental illness. On one hand this is a very beautiful phenomenon because it allows us to be what we are, this magnificent species with very special cognitive capacities in nature. But it is also a finely regulated phenomenon that when it is altered, generates these disorders or mental illnesses.”      

Hiram studied to be a Pharmacobiological Chemist – in other countries called biochemistry. Then he completed his master’s degree in physiology at the State University of Puebla and he received his PhD in Chemical Biological Sciences at the National Polytechnic Institute in Mexico. All of his studies, including his, bachelor’s, master’s and doctoral theses were in neuroscience. “My interest in science is what happens with brain plasticity for brain development and what happens when this brain plasticity is altered, which is a risk factor for mental illnesses, then understand how our brain adapts to form adequate connections for its functioning and then what happens when these connections are altered.”

He studies mainly through rodents, which allows them to study very specific mechanisms of brain development and mental illness at the level of plasticity. “Although it is impossible to reproduce a mental illness in rodents, both humans and rodents have a brain in which reality perception occurs, enabling surveillance. For example, both human and rodents must interpret the location of food and signals of warning, such as suspicious behavior of somebody in a dark and lonely street for humans, or the presence of a large moving object that may be a predator for rodents,” Hiram explains.

The studies give insight in the effects of the drugs used for mental illnesses: “We are interested to see what the drugs we use for the treatment of these mental illnesses do to brain plasticity. That has been our greatest scope as research, we have shown that beyond the conventional mechanisms of these drugs there are effects at the level of plasticity. In order to be able to develop new, more effective and safer drugs, brain plasticity could be a target in the future,” explains the Mexican researcher and goes with an example about the poor effects of the medicine:  “Now they’re about other things: neurotransmitters, dopamine, serotonin. These drugs are generally effective, but specifically for depression and schizophrenia, more than 30% of patients at a global level do not respond to the pharmacological treatment. I’ve always thought about it like this, what if you go to the doctor for some complication and they tell you well, the treatment is going to work, but only in a third of the cases. Well, that’s what happens with these drugs for mental illnesses, that’s something we have to improve,” says the Mexican researcher.

100 year old Nobel-inspiration    
Hiram recalls an important moment with his motivation for neuroscience when he volunteered in a neuropsychiatry lab: “It was there that I saw neurons under the microscope for the first time. We were using a technique known as the Golgi-technique, which was used by Santiago Ramón y Cajal more than 100 years ago (Nobelprize in Medicine 1906) to describe the theory of neural networks and which won him the Nobel Prize. Seeing it there in a microscope was like wow, seeing a neuron and in its morphology with the dendritic spines, imagining remembering all that I had read about this neuronal theory of Santiago Ramón y Cajal. Then I said – I would like to know more about these cells and how they work. That was the turning point that led me to become interested in neuroscience.”

Another role for the scientist – Awareness Days    
According to the Mexican researcher it is a common stigma that people with mental illnesses are to blame themselves for their condition. Something that does not happen as often with physical illnesses. He sees the role as a scientist also to work towards eliminating those stigmas: “I would like to do these awareness days on mental health or work on mental health, not only from this academic stage where I am now, academic research, articles and all that, but I think it is something I would like to develop in the future. Well, we study mental illnesses on a biochemical and neurophysiological level, but we are also aware that we have another problem, which we can also attack from our place as a scientist, right? OK, we do science, we do laboratory science, we go to congresses, but there is also a human side that we sometimes forget, we sometimes leave it aside,” says Hiram.

Social stigma of mental illnesses    
The Mexican researcher is also really worried about the social stigma he sees towards mental illnesses: “At the university level we are very used to hearing words like “you’re tired”. Hey, you have a lot of homework? We start to normalize having an anxiety attack or having an episode of depression as a normal part of being a university student, instead of seeking professional help,” says Hiram and continues: “The primary stigma associated with mental illness is denial. Believing that they do not exist or that no treatment (pharmacological or psychological) is necessary only exacerbates the condition. Also, some words used in mental illness diagnosis carry a negative social connotation. A clear example is schizophrenia, as this term is often used to describe people who speak or act nonsensically,” says the Mexican researcher.
He points out how Latin American countries, like his homeland, are falling behind on several points, for instance regarding diagnosis of mental illnesses. “The diagnosis of mental illnesses is purely clinical, without any laboratory or imaging tests to help to confirm it. This sometimes makes de diagnosis ambiguous and, consequently, the treatment as well. A contrasting example can be drawn with diabetes mellitus. A patient may present with symptoms of the disease. However, the disease is confirmed with a blood laboratory test that assesses the patient’s glucose metabolism and confirms the diagnosis. In many countries in Europe and the United States some specific risk factors (both, genetic and environmental ones) for mental illnesses have been detected which makes the diagnosis more specific. But in countries like Mexico we don’t have that. And so, it is like a little snowball with mental illnesses that is growing,  the lack of a precise and exact diagnosis, and so, it is like a little snowball with mental illnesses that is growing”.
And that again, obviously, has consequences for giving the right treatment: “The treatment is often not the right one, and these treatments have been acting on the same thing since the 60s. They only change the way in which it is dosed, but in the field of mental illnesses, there have not been treatments that are specifically disruptive. Well in depression, yes, currently we know a lot about ketamine which has a fast action on the symptoms of depression and curiously it has been shown that it seems that its activity as a fast-acting antidepressant is because it acts at the level of brain plasticity. This is still under debate, but I think that is the tip of the iceberg on plasticity and mental illnesses, I think we already have a panorama of plasticity in mental illnesses, which is very promising,” says Hiram.

Disparity in access to new drugs and powerful microscopes                                                                                                                  And being able to research on the human brain is quite a big challenge, says the Mexican scientist: “Studying plasticity in patients still has many technical limitations. We don’t have equipment that allows us to see this plasticity in real time, like an echocardiogram. There we can see the function of the heart in real time under different conditions. Plasticity is still inaccessible to us in a patient, hence the importance of animal models to study this, because these models allow us to see plasticity in real time, from proteins that are in the synapse, to the behavior of the animal. It allows us to create a mapping of what might be happening with this plasticity at both physiological and pathological levels and that has led us to understand, what is its role in neurodevelopment and also, what is its probable error in the pathophysiology of mental illnesses that is happening in these people at the level of plasticity.”
“I think the biggest challenge is that in general, neuroscience is a field that is very much in vogue all over  . But in countries like Mexico, which do not have an infrastructure and do not have large budgets for these new technologies for the study of the brain, new developed technologies are somewhat inaccessible here. Mainly because it’s expensive, these devices, for example, there are microscopes (multiphoton ones) in which we could see plasticity in real time with very innovative techniques. Well, we don’t have the capacity to buy that microscope, I think that in Mexico there must be a few multiphoton microscopes in the whole country. And well, there are universities, that is the equipment that they have in the United States here in Europe that just one university has two or three of these microscopes. So, that is the disparity we are facing”.

For Hiram in some sense it is all about funding: “Ultimately, it all boils down to money: having it allows you to conduct and publish cutting-edge research (as publishing a research paper can cost up to 2000 USD), while lacking it keeps you in the shadow of those who can.” Due to budget constraints, collaboration with other groups is essential to carry out projects, according to Hiram. He has conducted research in collaboration with groups not only in the same university but also from other national universities, including UNAM, IPN, CINVESTAV as well as international universities such as Complutense University of Madrid in Spain.

But the disparity is not only negative, insist Hiram: “That also opens up an opportunity for us to do things that are more creative, what I mainly think can be an advantage in this initial part of my career as an independent researcher is precisely to postulate new models to interrupt neurodevelopment that have relevance at the clinical level. So, we don’t have access to these great tools, but we are motivated by creativity to be able, for example, to generate some animal models that do not involve, well, more than the purchase of a drug. O making models that have to do with the environment, for example stress as a risk factor, that allow us to generate things so that mental illnesses can be studied”.

Lise Josefsen Hermann met Hiram Tendilla Beltran at the annual Lindau Nobel Laureate meeting 2023.                              Lise is a freelance journalist based in Latin America for more than a decade. She is a Pulitzer Grantee, works for the investigative media Danwatch and  has published in media like Al Jazeera, BBC, Deutsche Welle, Danish Broadcasting Corporation, El Pais, New York Times, and Undark Magazine

Hiram Tendilla-Beltran
Hiram Tendilla-Beltrán with Guy Hindley, Institute of Clinical Medicine, University of Oslo.
Hiram Tendilla-Beltrán with other Mexican scientists in the Lindau Nobel Laureate Meeting 2023.