Fine-tuning communication: How drugs and diseases influence signals between nerve cells

Nerve cells communicate with one another via signaling molecules. The rule is: the more of these molecules, the stronger the signal. Drugs and diseases influence these processes and can weaken or strengthen the signal. Together with colleagues of Einstein BIH Visiting Fellow Thomas Südhof from Stanford University, who won the Nobel Prize in Medicine in 2013 and is supported by Stiftung Charité, Charité researchers have now been able to explain how these communication “modulators” work. They have published their results in the scientific journal Cell.

The most common signaling molecule in the brain is a neurotransmitter called glutamate. So-called modulatory neurotransmitters such as adrenaline, dopamine, and serotonin use glutamate to influence the signal transmission and thus change our perception, our feelings, and our actions. All psychoactive drugs also take effect via this modulatory system, which is disrupted in many psychiatric illnesses such as depression or addiction.

Researchers led by Berlin neurophysiologist Professor Christian Rosenmund from Charité – Universitätsmedizin Berlin and U.S. colleagues led by Einstein BIH Visiting Fellow Thomas Südhof, 2013 Nobel Prize winner in Medicine, have now discovered how this neuromodulatory system works. “We were able to show that the molecule synapsin plays an important role in this process,” says Dr. Christopher Patzke, co-lead author of the paper and a postdoc in Südhof’s laboratory. “It sits on the surface of the synaptic vesicles and changes shape due to the effects of various neuromodulators. This leads to the vesicles in the synapses either joining together and releasing more messenger substances – which strengthens the signal – or withdrawing from the synapse and releasing fewer signaling molecules – which weakens the signal.”

Scientists were able to observe these processes for the first time thanks to a new technique developed by Rosenmund’s laboratory: “We electrically stimulate isolated nerve cells and then shock-freeze them at a very precise moment with liquid nitrogen,” explains co-lead author Dr. Marisa Brockmann, a postdoc in Rosenmund’s lab. “Under the electron microscope, we are then able to observe the tiny, ultrafast movements as if they are playing in slow motion.”

Nobel laureate Thomas Südhof is delighted with the successful collaboration. ‟We know that mutations in the SYN1 gene can cause developmental disorders, epilepsy, and autism. Our work helps now to understand why this is the case and has also opened up a potential pathway that can be targeted in drug treatment.”

“This work is not only of fundamental importance in understanding the function of our brain, it also shows how the synapse function can be disrupted in psychiatric diseases,” says Christian Rosenmund (ECN Member). “Our collaborating laboratories have perfectly complemented each other in our work on this topic, and we are happy and very grateful to have institutions like Stiftung Charité, the Einstein Foundation Berlin, and the Berlin Institute of Health that allow us to collaborate in this exciting research project.”

Professor Axel Radlach Pries, interim Chairman of the BIH Executive Board and Dean of Charité – Universitätsmedizin Berlin, expressed his delight at the current publication in the journal Cell: “The brilliant work by Christian Rosenmund and Thomas Südhof reinforces our belief that it’s a good idea to bring together outstanding minds at the Berlin Institute of Health.”

Stiftung Charité has since 2014 been enabling high-level scientists to do research at the BIH through its Johanna Quandt Private Excellence Initiative. The aim of the initiative is to give scientists an opportunity to pursue innovative research projects and to help the BIH build a network of contacts with outstanding scientists and their home institutions, thus pushing forward biomedical research in Germany while also enhancing Berlin’s position as an outstanding science location.

Literature
Patzke et al. (2019): "Neuromodulator Signaling Bidirectionally Controls Vesicle Numbers in Human Synapses", Cell, https://doi.org/10.1016/j.cell.2019.09.011

Source: https://bit.ly/2NFdoZe

 

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