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David Engblom

Associate prof. Linköping University Medicine Year of admission: 2012

Mapping the neurobiology behind feelings of unease
In diseases such as rheumatism, tuberculosis and AIDS, the body is inflamed. The signal molecules of the immune system also affect the brain and contribute to low spirits and depression. As a Wallenberg Academy Fellow, David Engblom is trying to map the neurobiological basis of such feelings of unease.

Long ago, the Greek poet Archilochus once coined the comparison that the fox knows many things, but the hedgehog knows one big thing. David Engblom undoubtedly identifies with the hedgehog. For him, it is important to do things properly. He prefers to go to the depths instead of jumping around between many different questions.
"If I get interested in a question, I have a tendency to stick to it. Sometimes, it is a weakness, but often I think that it is a strength."
His choice of profession, research, he describes with expressions such as intellectually challenging, insanely fun and addictive. He wants to make a difference and when his career is over, he hopes to be able to look back and confirm that the world would actually have been worse off without his research contribution.
At the same time, David Engblom believes that success in research is not only about knowledge and wisdom, but also coincidence and luck.
"Research is a bit like walking in a search party. You can do a good job even if you don't find anything since you simply ended up at the wrong place in the search party. It is not always the case that a person who actually finds something did a better job than the others, but rather everyone in the search party is needed."
David Engblom more or less slid into the research after his third year at medical school. He was taking a research-preparatory course, found it enjoyable and began working in a research project on the summers. The project went somewhat poorly, which made him angry and extra motivated. Then he became a doctoral student and it also went poorly in the beginning, but it gradually improved and he ultimately ended up in a good situation.
"I can willingly admit that I was lucky as a doctoral student. I simply ended up in a good project, which meant that it also went well for me. I also really enjoyed it."
The original plan, which was to finish the doctoral degree and then return to medical school, was shelved. He chose the research profession, something he has never regretted.
In his doctoral project, David Engblom worked with the question: how can the brain know that it should trigger a fever? The area still interests him, but the original question has been developed a bit since then. As a Wallenberg Academy Fellow, his research is mainly about how signal molecules, intermediaries, that activate the immune system can also contribute to symptoms like low spirits, depression and a loss of appetite. He will also study the connection between inflammation, negative thoughts and drug addiction, and also why drugs are actually so addictive.
"It is very positive. Firstly, it is a stamp of quality, a proof that people believe in what we are doing. Secondly, it enables a financial long-term approach. I think it is very sound to allow things to take time in research, it means that one can really finish the job and do things well before publishing. Then it is also important to networking and I have been able to meet many dynamic people in this group of fellows."
Reward and punishment
In the brain's so-called "mesolimbic system", there are nerve cell groups, circuits, that upon stimulation give rise to emotions of pleasure and reward and other nerve cell groups that upon stimulation give rise to feelings of unease and punishment.
"Regularly, these systems are in balance with each other, but sometimes the balance can be shifted in one direction or the other. For example, addictive drugs overactivate and ‘hijack’ the reward system, which leads to a morbid craving for the drug. Diseases, including inflammatory conditions such as rheumatism, AIDS and tuberculosis, can also upset the balance between the systems.”
The challenge that spurs David Engblom is to understand how this takes place, meaning to understand the neurobiological basis of experiences of reward or punishment. The chain between cause and effect is long and complicated and, besides the brain, also includes full-body physiology, including the immune system, blood circulation, and peripheral nerves.
"First, we have to identify which of the inflammatory substances is secreted by the immune system, which is important to trigger the various inflammatory symptoms. The next step is to understand how these substances go from the body into the brain. This can be via a nerve or also via small blood vessels. We know, for example, that cytokines bind to the blood vessels' endothelial cells and that these cells in turn secrete prostaglandins in the brain.”
Thereafter, one tries to understand which nerve cell groups the prostaglandins bind to or what nerve cell groups that are reached by neural messages from nerves that lead into the brain from the body. They are then inside the mesolimbic system where changes in the release of signal substances, such as dopamine, serotonin and endogenous opioids trigger emotions of well-being and unease.
"We work with cell type specific modifications in mutated mice that, for example, are missing certain receptors that the signal substances bind to. The mice receive an inflammatory stimulus and then we observe their behavior using a model that is called conditioned place aversion.”
Based on the observations, David Engblom and his colleagues then solve the puzzle and understand what the connection between cause and effect looks like.
"The brain is a like a large book that is ready to be read. Being able to connect something that happens at a molecular level and nerve cell group level to something on recognizes in one's own behavior and thoughts - that's cool."
Text Anders Esselin
Translation Semantix
Photo Magnus Bergström

Long ago, the Greek poet Archilochus once coined the comparison that the fox knows many things, but the hedgehog knows one big thing. David Engblom undoubtedly identifies with the hedgehog. For him, it is important to do things properly. He prefers to go to the depths instead of jumping around between many different questions.

If I get interested in a question, I have a tendency to stick to it. Sometimes, it is a weakness, but often I think that it is a strength.

His choice of profession, research, he describes with expressions such as intellectually challenging, insanely fun and addictive. He wants to make a difference and when his career is over, he hopes to be able to look back and confirm that the world would actually have been worse off without his research contribution.

At the same time, David Engblom believes that success in research is not only about knowledge and wisdom, but also coincidence and luck.

Research is a bit like walking in a search party. You can do a good job even if you don't find anything since you simply ended up at the wrong place in the search party. It is not always the case that a person who actually finds something did a better job than the others, but rather everyone in the search party is needed.


Angry and extra motivated

David Engblom more or less slid into the research after his third year at medical school. He was taking a research-preparatory course, found it enjoyable and began working in a research project on the summers. The project went somewhat poorly, which made him angry and extra motivated. Then he became a doctoral student and it also went poorly in the beginning, but it gradually improved and he ultimately ended up in a good situation.

I can willingly admit that I was lucky as a doctoral student. I simply ended up in a good project, which meant that it also went well for me. I also really enjoyed it.

The original plan, which was to finish the doctoral degree and then return to medical school, was shelved. He chose the research profession, something he has never regretted.

In his doctoral project, David Engblom worked with the question: how can the brain know that it should trigger a fever? The area still interests him, but the original question has been developed a bit since then. As a Wallenberg Academy Fellow, his research is mainly about how signal molecules, intermediaries, that activate the immune system can also contribute to symptoms like low spirits, depression and a loss of appetite. He will also study the connection between inflammation, negative thoughts and drug addiction, and also why drugs are actually so addictive.

Reward and punishment

In the brain's so-called mesolimbic system, there are nerve cell groups, circuits, that upon stimulation give rise to emotions of pleasure and reward and other nerve cell groups that upon stimulation give rise to feelings of unease and punishment.

Regularly, these systems are in balance with each other, but sometimes the balance can be shifted in one direction or the other. For example, addictive drugs overactivate and ‘hijack’ the reward system, which leads to a morbid craving for the drug. Diseases, including inflammatory conditions such as rheumatism, AIDS and tuberculosis, can also upset the balance between the systems.

The challenge that spurs David Engblom is to understand how this takes place, meaning to understand the neurobiological basis of experiences of reward or punishment. The chain between cause and effect is long and complicated and, besides the brain, also includes full-body physiology, including the immune system, blood circulation, and peripheral nerves.

First, we have to identify which of the inflammatory substances is secreted by the immune system, which is important to trigger the various inflammatory symptoms. The next step is to understand how these substances go from the body into the brain. This can be via a nerve or also via small blood vessels. We know, for example, that cytokines bind to the blood vessels' endothelial cells and that these cells in turn secrete prostaglandins in the brain.

Thereafter, one tries to understand which nerve cell groups the prostaglandins bind to or what nerve cell groups that are reached by neural messages from nerves that lead into the brain from the body. They are then inside the mesolimbic system where changes in the release of signal substances, such as dopamine, serotonin and endogenous opioids trigger emotions of well-being and unease.

We work with cell type specific modifications in mutated mice that, for example, are missing certain receptors that the signal substances bind to. The mice receive an inflammatory stimulus and then we observe their behavior using a model that is called conditioned place aversion.”

Based on the observations, David Engblom and his colleagues then solve the puzzle and understand what the connection between cause and effect looks like.

The brain is a like a large book that is ready to be read. Being able to connect something that happens at a molecular level and nerve cell group level to something on recognizes in one's own behavior and thoughts - that's cool.

 

Limbic system: A complex of nerve cells on the inside of the brain's two hemispheres with a substructure in each temporal lobe. Also known as the emotional brain.

Dopamine: One of the most important signal substances in the central nervous system. Dopamine occurs in the mesolimbic system, among others.

Prostaglandins: Hormone-like substances that affect local blood circulation and have a mucous-membrane protective effect in the gastrointestinal tract. In inflammation, they contribute to vasodilation and strengthening of the impulse formation in pain nerve branches. They also affect the brain's thermostat that regulates body temperature.

Cytokines: Small proteins that are produced by the immune system as a response to an infection. They work as signal molecules between cells and stimulate production and differentiation of lymphocytes, for instance.

 

Text: Anders Esselin
Translation: Semantix
Photo: Magnus Bergström