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Brain plasticity and the link to depression

network of neurons: Illustration
Illustration: iStock/koto_feja.

This year's prestigious Segerfalk lecture will be given by Eero Castrén, Research Director at the Neuroscience Centre at the University of Helsinki. In his research on brain plasticity, he has discovered clues about which mechanisms in the brain are affected by antidepressants – and they could explain why these medicines work.

Eero Castrén conducts research on brain plasticity and is primarily interested in how neurons interact with each other. What controls this interaction, how can the contact between neurons be modified – and when this is done, what is the result? Signal substances in the brain play an important role in this. 
 
“Signal substances are critical for brain plasticity and determine which connections are activated in the brain. For example, if you learn something, certain neurons will be activated and the synapses to which they connect become stable, creating a memory. When the same synapses are repeatedly activated by the same event, a network of neurons is created that connects to this particular event,” Eero Castrén explains. 
 
More than 20 years ago, the questions surrounding how the interaction of neurons affects plasticity led Eero Castrén to take an interest in how plasticity is affected by the drugs used in brain diseases. He studied, among other things, what happens during the release of antidepressants in the brain. 

At first, I had difficulty believing what we were seeing. I had four different doctoral students examine this, independently of each other.

In severe depression, the brain’s signalling system is affected and the levels of signal substances such as serotonin, dopamine and noradrenaline are altered. Exactly what happens or what triggers the depression is unclear though. However, it is known that many people get better with drugs that raise the levels of serotonin in the brain. It is also known that they lead to higher levels of serotonin in the brain in direct connection with the onset of taking the medicines, however, there is a big question mark over why the effect of the drug – improvement – is only observed after a few weeks.

Help brain cells to communicate and grow

Eero Castrén’s research on the signal substance BDNF could provide an interesting clue. It turns out that taking antidepressants releases BDNF, which helps brain cells to communicate and grow. Together with his research team, Eero Castrén demonstrated that antidepressants bind directly to the BDNF receptor. In studies, they have also demonstrated that when you interrupt the connection between the antidepressant drug and the receptor in mice and cells, the antidepressant effect is blocked. 

“At first, I had difficulty believing what we were seeing. I had four different doctoral students examine this, independently of each other. Their results pointed to the same thing. There are those who are sceptical of our results and that is understandable. Other researchers need to confirm this. It is not easy to study whether the mechanism is active during the improvement phase of depression. We also do not know which cell types are affected, but we have been able to demonstrate that antidepressants slowly affect brain plasticity.”

There are also other things to suggest that the theory could be right. One is anaesthetic ketamine, which has been shown to help severe depression in people who do not respond to standard drug treatment. Ketamine also leads to an increase in the levels of the receptor for BDNF in the brain.
 
“Ketamine binds to the same receptor that is affected by antidepressants. The fact that ketamine seems to work much faster may be related to the fact that it binds more firmly. However, we do not know that yet.” 

How the brain is shaped and reorganised according to the demands

Although his research has a focus on depression, Eero Castrén is careful to point out that he is not a depression researcher. He cannot answer whether the mechanism in the brain can explain why exercise is a protective factor against depression, or whether it also explains possible side effects of the medicine. His research area is plasticity. Put simply, plasticity is how the brain is shaped and reorganised according to the demands placed on it. This has to do with how neurons interact with each other, but also how they can be affected – and if so, 
what that leads to. 
 
Eero Castrén initially studied to become a doctor but became interested in research. A couple of lucky coincidences and a courage to say yes have led him to where he is now. He loves the research profession:
 
“You get the opportunity to discover new things that were previously unknown. You get to work with the brain. And you get to work with enthusiastic people. You work with young people and can follow their development. Could it be any better?”

Facts on BDNF

BDNF, Brain Derived Neutrophic Factor, is a protein that is important in the development of neurons and the function of the brain. It binds to the TRKB receptor, which is found on the surface of many brain cells. When binding occurs, signalling pathways are created that affect brain plasticity and the function and growth of brain cells. 

Neuroscience Day 2022, May 5th

eero castrén. photo.

Segerfalk lecture by Eero Castrén, Research Director at the Neuroscience Centre at the University of Helsinki, Finland.

Title: "Neuronal plasticity, neurotrophin signaling and the mechanism of action of the common antidepressant drugs"

Link to program Neuroscience Day 2022

 

The Neuroscience of Empathy and Compassion Conference, May 4th

Birgit Rausing Centre for Medical Humanities and the Segerfalk Foundation proudly present The Neuroscience of Empathy and Compassion Conference, May 4th, 2022.

The Neuroscience of Empathy and Compassion Conference brings together leading scientists who have all contributed to elucidating various facets of empathy and compassion, their neural correlates and functions.

The conference is aimed at the neuroscience community, psychologists, and healthcare professionals, as well as researchers in social sciences and the humanities.

Link to conference web site