February 19, 2021, 12:14 pm
Research results, scientific publications
Freiburg researchers, together with international colleagues, find a new mechanism by which antidepressants work in the brain / discovery enables the development of new therapies / publication in the specialist magazine Cell
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Scientists at the University Medical Center in Freiburg, together with international colleagues, have shown that antidepressants attach to nerve cells in a previously unknown location and thus develop their mood-enhancing effect. By binding to the receptor of the so-called brain-derived neurotrophic factor (BDNF) on the nerve cells, there is an improved activity in brain regions that are impaired in depressed patients. It worked particularly well when the cholesterol level in the blood was normal. The findings now enable a targeted search for active ingredients that bind to the BDNF receptor. The study was published on February 18, 2021 in the renowned specialist magazine Cell.
“With the BDNF receptor as a docking point, we can for the first time directly explain how antidepressants work and why it takes so long for the effect to set in,” explains Prof. Dr. Claus Normann, research group leader at the Clinic for Psychiatry and Psychotherapy at the Freiburg University Medical Center. Until now it was assumed that they act by increasing the messenger substance serotonin in the brain; however, it remained completely unclear exactly how this works.
For the first time there is a direct link between the molecular and clinical effect
That is now changing with the study of an international working group in collaboration with Normann, Dr. Stefan Vestring and Dr. Tsvetan Serchov from the Department of Psychiatry and Psychotherapy at the Freiburg University Medical Center. In their research, they were able to show in mice that antidepressants bind directly to the receptor for the growth hormone BDNF. This leads to an improved activity in brain regions that are impaired in depressed patients. This applies to different types of antidepressants such as Selective Serontonin Reuptake Inhibitors, SSRIs for short, or Ketamine.
Active ingredients facilitate learning and the perception of positive information
“By stimulating the BDNF, the brain can better absorb new, positive information from the environment or during psychotherapy and recovers from its depressed state,” says Normann. The researchers showed that the antidepressants intervene via the BDNF receptor in a central learning and adaptation mechanism of the brain known as synaptic plasticity. “Interestingly, this binding site needs a normal cholesterol level in order to be able to be optimally active.” As the team showed, high, but also too low cholesterol levels deform the BDNF receptor so that the active ingredients bind more poorly.
These findings form an important basis for understanding depression and developing new drugs. Targeted therapy could open up new perspectives for a more effective treatment of severe depression with fewer side effects.
Scientific contact:
Prof. Dr. Claus Normann
Managing Senior Physician
Clinic for Psychiatry and Psychotherapy
university hospital Freiburg
Phone: 0761 270-66340
[email protected]
Originalpublikation:
Original-Titel der Studie: Antidepressants act by directly binding to TRKB neurotrophin receptors
DOI: 10.1016/j.cell.2021.01.034
Link to the study: https://authors.elsevier.com/sd/article/S0092-8674(21)00077-5
Further information:
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