Event type
Dissertations
Doctoral thesis defence: Erik von Oelreich

19-11-2021 9:00 am Add to iCal
Campus Solna
Location
Torsten Gordh Auditorium, S2:02, Norrbacka, Karolinska University Hospital, Solna
Lead

Long-term outcomes after trauma and intensive care

Content

Title

"Long-term outcomes after trauma and intensive care"

Author

Erik von Oelreich, Department of Physiology and Pharmacology

Supervisor

Anders Oldner, adjunct professor, Department of Physiology and Pharmacology

Co-supervisor

Emma Larsson, Department of Physiology and Pharmacology

Mikael Eriksson, Department of Physiology and Pharmacology

Abstract

Read the Abstract here

Contact

Event type
Dissertations
Dissertation: Carl-Fredrik Bowin

12-11-2021 9:00 am Add to iCal
Campus Solna
Location
Eva & Georg Klein, Biomedicum, Solnavägen 9, Karolinska Institutet, Solna
Lead

Welcome to Carl-Fredrik Bowin's doctoral thesis defence with the title "RWNT/Frizzled signaling : illuminating the road towards pathway selectivity".

Content

Doctoral Student

Carl-Fredrik Bowin

Title

"RWNT/Frizzled signaling : illuminating the road towards pathway selectivity"

Supervisor

Professor Gunnar Schulte, Department of Physiology and Pharmacology, Karolinska Institutet

Abstract

Read it here

Contact

Event type
Dissertations
Doctoral thesis defence: Paula da Silva

27-10-2021 10:00 am Add to iCal
Campus Solna
Location
Eva & George Klein Auditorium, Biomedicum, Solnavägen 7, Karolinska Institutet, Solna and zoom
Lead

Welcome to Paula da Silvas Doctoral thesis defence titled: "Mechanisms of inter-organ crosstalk mediated by tryptophan metabolism", Wednesday October 27th at 10 am.

Content

Title

"Mechanisms of inter-organ crosstalk mediated by tryptophan metabolism"

 

Abstract

Read the Abstract here

 

Supervisor

Jorge Ruas, Professor FyFa, Karolinska Institutet

 

Co-supervisor 

Katarina Gradin, CMB, Karolinska Institutet

Duarte Ferreira, Assistant Professor FyFa

 

Zoomlink

To be published soon

 

Contact

Event type
Half-time controls
Half time seminar: Peter Tedeholm

17-09-2021 1:00 pm Add to iCal
Online
Location
Zoom
Lead

Welcome to the half time review for Peter Tedeholm, Friday September 17, at 1 pm.

Content

Title

"Predictors of selection process and work-related characteristics within counterterrorism intervention units”.

 

Supervisor

Ph.D, MD Agneta Larsson, Department of Physiology and Pharmacology, Karolinska Institutet

 

Co-supervisors

Associate Professor Anders Sjöberg, Department of Psychology, Stockholm University

Ph.D. Irene Lund, Department of Physiology and Pharmacology, Karolinska Institutet

Professor Elkhonon Goldberg, School of Medicine, New York University                

 

Half-time board

Professor Ole Boe, Department of Business, Strategy and Political Sciences, School of Business, Campus Drammen

Professor Martin Bäckström, Department of Psychology, Lund University

Associate professor Johnny Hellgren, Department of Psychology, Stockholm University

Online meeting

Zoom link here

Contact

Event type
Lectures and seminars
"Working memory 2.0" - a lecture with Earl K. Miller

21-09-2021 4:00 pm Add to iCal
Online
Location
Online via Zoom (https://ki-se.zoom.us/j/66543668821)
Lead

Welcome to a lecture with Earl K. Miller, at The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, USA, on Tuesday 21 September 2021 at 16:00. The lecture will be held online via Zoom.

Content

Title

"Working memory 2.0"

Presenter

Earl K. Miller, The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, USA

Abstract

Working memory is the sketchpad of consciousness, the fundamental mechanism the brain uses to gain volitional control over its thoughts and actions. For the past 50 years, working memory has been thought to rely on cortical neurons that fire continuous impulses that keep thoughts “online”.  However, new work from our lab has revealed more complex dynamics.  The impulses fire sparsely and interact with brain rhythms of different frequencies.  Higher frequency gamma (> 35 Hz) rhythms help carry the contents of working memory while lower frequency alpha/beta (~8-30 Hz) rhythms act as control signals that gate access to and clear out working memory.  In other words, a rhythmic dance between brain rhythms may underlie your ability to control your own thoughts.

Hosts

Henrik Ehrsson & Konstantina Kilteni, Department of Neuroscience

Via Zoom

Join the meeting via Zoom

Contact

Event type
Lectures and seminars
"Free will in the human brain?" - a lecture with Patrick Haggard

22-09-2021 4:00 pm Add to iCal
Campus Solna
Location
Eva & Georg Klein Lecture Hall (aka Biomedicum 1), Solnavägen 9, Solna
Lead

Welcome to a lecture with Patrick Haggard, Institute of Cognitive Neuroscience, University College London, UK, on Wednesday 22 September 2021 at 16:00 in Biomedicum.

Content

Title

"Free will in the human brain?"

Presenter

Patrick Haggard, Institute of Cognitive Neuroscience, University College London, UK

Abstract

The capacity for voluntary action ("free will") is often viewed as fundamental to human nature but is difficult to explain scientifically. The strongest neuroscientific consensus perhaps comes from drawing a contrast between voluntary actions and reflexes. But this does not positively say what a voluntary action is, and how the brain produces it. I will review three current ideas about volition, based on randomness, on value, and on problem-solving, respectively. I will discuss the relation between volition and consciousness, and I'll describe the difficulties of searching for neural correlates of volition in human experiments. I'll end with experimental EEG results suggesting that recent attempts to eliminate volition from neuroscience may be premature.

Hosts

Henrik Ehrsson & Konstantina Kilteni, Department of Neuroscience

Contact

Event type
Half-time controls
Half time seminar: Koshiar Medson

22-09-2021 4:00 pm Add to iCal
Online
Location
Zoom
Lead

Welcome to the half time review for Koshiar Medson, Wednesday September 22, at 4 pm.

Content

Titel

"Clinical applications of MRI in diagnosis of pulmonary embolism"


Main Supervisor

Peter Lindholm, Department of Physiology and Pharmacology, Karolinska Institutet


Co Supervisor

Eli Westerlund, Medicine, Karolinska Institutet

Contact

Event type
Half-time controls
Half time seminar: Albin Sjöblom

06-10-2021 1:00 pm Add to iCal
Campus Solna
Location
J5:12 Greitzrummet
Lead

Welcome to the half time review for Albin Sjöblom. Wednesday October 6 at 1 pm.

Content

Titel

"Clinical and physiological consequences of preoxygenation using high flow nasal oxygen in emergency anesthesia"


Main Supervisor

Doc Malin Jonsson Fagerlund, Department of Physiology and Pharmacology, Karolinska Institutet


Co Supervisors

Med Dr Magnus Hedberg, Department of Physiology and Pharmacology, Karolinska Institutet

Prof Lars I Eriksson, Department of Physiology and Pharmacology, Karolinska Institutet


Half time board

Doc Sophie Lindgren, University of Gothenburg

Doc Åke Norberg, CLINTEC, Karolinska Institutet

Doc Johan Petersson, Department of Physiology and Pharmacology, Karolinska Institutet

Attend online

Zoomlink here

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Published: 2021-08-11 02:00 | Updated: 2021-08-11 09:50

New findings on how ketamine acts against depression

Illustration of depression.
Illustration: Getty Images.

The discovery that the anaesthetic ketamine can help people with severe depression has raised hopes of finding new treatment options for the disease. Researchers at Karolinska Institutet have now identified novel mechanistic insights of how the drug exerts its antidepressant effect. The findings have been published in the journal Molecular Psychiatry.

Portrait photo of Per Svenningsson, professor at the Department of Clinical Neuroscience
Per Svenningsson. Photo: Ulf Sirborn.

According to the World Health Organization, depression is a leading cause of disability worldwide and the disease affects more than 360 million people every year.

The risk of suffering is affected by both genetics and environmental factors. The most commonly prescribed antidepressants, such as SSRIs, affect nerve signalling via monoamines in the brain.

However, it can take a long time for these drugs to help, and over 30 percent of sufferers experience no relief at all.

The need for new types of antidepressants with faster action and wider effect is therefore considerable.

An important breakthrough is the anaesthetic ketamine, which has been registered for some years in the form of a nasal spray for the treatment of intractable depression.

Relieves depressive symptoms quickly

Unlike classic antidepressants, ketamine affects the nerve signalling that occurs via the glutamate system, but it is unclear exactly how the antidepressant effect is mediated. When the medicine has an effect, it relieves depressive symptoms and suicidal thoughts very quickly.

However, ketamine can cause unwanted side effects such as hallucinations and delusions and there may be a risk of abuse so alternative medicines are needed.

The researchers want to better understand how ketamine works in order to find substances that can have the same rapid effect but without the side effects.

Explains ketamine's effects

In a new study, researchers at Karolinska Institutet have further investigated the molecular mechanisms underlying ketamine's antidepressant effects. Using experiments on both cells and mice, the researchers were able to show that ketamine reduced so-called presynaptic activity and the persistent release of the neurotransmitter glutamate.

"Elevated glutamate release has been linked to stress, depression and other mood disorders, so lowered glutamate levels may explain some of the effects of ketamine," says Per Svenningsson, professor at the Department of Clinical Neuroscience, Karolinska Institutet, and the study’s last author.

When nerve signals are transmitted, the transmission from one neuron to the next occurs via synapses, a small gap where the two neurons meet.

The researchers were able to see that ketamine directly stimulated AMPA receptors, which sit postsynaptically, that is, the part of the nerve cell that receives signals and this leads to the increased release of the neurotransmitter adenosine which inhibits presynaptic glutamate release.

The effects of ketamine could be counteracted by the researchers inhibiting presynaptic adenosine A1 receptors.

"This suggests that the antidepressant action of ketamine can be regulated by a feedback mechanism. It is new knowledge that can explain some of the rapid effects of ketamine," says Per Svenningsson

In collaboration with Rockefeller University, the same research group has also recently reported on the disease mechanism in depression.

The findings, also published in the journal Molecular Psychiatry, show how the molecule p11 plays an important role in the onset of depression by affecting cells sitting on the surface of the brain cavity, ependymal cells, and the flow of cerebrospinal fluid.

Publications

“Ketamine decreases neuronally released glutamate via retrograde stimulation of presynaptic adenosine A1 receptors”, Vesna Lazarevic, Yunting Yang, Ivana Flais, Per Svenningsson. Molecular Psychiatry, 11 August 2021, doi: 10.1038/s41380-021-01246-3.

“Ependymal cells-CSF flow regulates stress-induced depression”, Ji-Seon Seo, Ioannis Mantas, Per Svenningsson and Paul Greengard. Molecular Psychiatry, 7 July 2021 doi: 10.1038/s41380-021-01202-1.

 

Published: 2021-06-02 16:20 | Updated: 2021-06-02 16:20

Analysis of 4,000 drugs reveals an alternative mechanism for a new anticancer therapy

By analyzing 4,000 drugs’ ability to affect cells’ capacity to produce proteins, researchers at Karolinska Institutet found that an anticancer therapy currently trialed in human patients works differently than previously thought. As many human diseases have alterations in this process called translation, the new knowledge contributes to a better understanding of how translation is regulated and the biological routes that regulate it. The study is published in PLOS Biology.

Oscar Fernandez Capetillo, Professor in Cancer Therapy. Photo: Martin Stenmark

Translation is the reaction by which cells produce new proteins, the elements they need to perform all their functions. This important process is frequently reduced or increased in human disease.

“In this context, we tried to provide a panoramic catalogue that details how currently available medicines, as well as others that are under development, affect translation in living human cells. We want to understand if we can boost translation with chemicals and if such chemicals could be of use for the treatment of diseases related to reduced translation”, says Oscar Fernandez-Capetillo, Professor of Cancer Therapy at the Department of Medical Biochemistry and Biophysics.

More than 4,000 drugs examined with High Throughput Microscopy

In this study, the researchers examined the effects of more than 4,000 drugs, which include the vast majority of medically approved drugs, as well as many others that are under clinical development. The drugs evaluated include compounds and medicines used in multiple diseases, including anticancer medicines.

The study was performed using High-Throughput Microscopy, a technology that enables the automatic acquisition and analysis of thousands of microscopy images.

Different mechanism behind new cancer therapy than previously thought

Besides providing a catalogue of how all of these drugs affect translation, the study led to an unexpected finding that is relevant in oncology. There is a class of drugs called “sphingosine kinase inhibitors” that were developed to inhibit a family of proteins known as Sphingosine Kinases. Previous works found that some of these drugs could kill cancer cells in vitro and in mice, and this led to the hypothesis that inhibiting the function of sphingosine kinases could be a new anticancer therapy. Some of these compounds are in fact being tested clinically in human cancer patients.

“Our work reveals that the toxicity of these compounds for cancer cells is actually not related to Sphingosine kinases, but to an effect of the drugs in the Endoplasmic Reticulum which becomes toxic. We believe that clarifying that the mechanism of action of a drug that is being given to human patients is different to the one previously thought is important”, says Oscar Fernandez-Capetillo.

The study is first to show how nearly all medically approved drugs affect the capacity of translation. Interestingly, no drugs were found to be capable of substantially increasing translation in cells grown with plenty of nutrients. It thus seems that identifying medicines that are capable to “boost” translation levels might be rather challenging.

The research was funded by grants from the Cancerfonden foundation and the Swedish Research Council (VR).

Publication

A chemical screen for modulators of mRNA translation identifies a distinct mechanism of toxicity for sphingosine kinase inhibitors.
Corman A, Kanellis DC, Michalska P, Häggblad M, Lafarga V, Bartek J, Carreras-Puigvert J, Fernandez-Capetillo O
PLoS Biol 2021 May;19(5):e3001263

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