Chronic stress can lead to depression and anxiety in humans. Scientists working with Herwig Baier, Director at the Max Planck Institute of Neurobiology in Martinsried, recently discovered a very similar link in fish. Normally, the stress hormone cortisol helps fish, as in humans, to regulate stress.
The zebrafish (Danio rerio) is a popular model organism for many questions in the field of genetics and developmental biology.
© MPI f. Neurobiology
Zebrafish with a mutation in the glucocorticoid receptor exhibit passive behaviour in a stressful situation. The behaviour returns to normal with a commercial antidepressant in the water. The findings demonstrate a significant correlation between stress regulation and mood disorders, one which evidently plays a central role in humans, too.
© Max Planck Institute of Neurobiology / Schorner
Fish that lack the receptor for cortisol as a result of a genetic mutation exhibited a consistently high level of stress. They were unable to adapt to a new and unfamiliar situation. The fishes’ behaviour returned to normal when an antidepressant was added to the water. These findings demonstrate a direct causal link between chronic stress and behavioural changes which resemble depression. The findings could also open the door to an effective search for new drugs to treat psychiatric disorders.
In stressful situations, the body releases hormones in order to ready itself for a fight or flight reaction. But it is equally important for the hormone level to return to normal after a certain time. If that does not happen, chronic stress can result, a condition that is linked to depression and anxiety, among other things. Whether stress is a trigger or merely a side effect of such affective disorders remains unclear.
The indication of a causal relationship between stress and depression comes from totally unexpected quarters. An international team led by Herwig Baierfrom the Max Planck Institute of Neurobiology in Martinsried and the University of California in San Francisco observed that zebrafish suffering from chronic stress as a result of a genetic mutation showed signs of depression in behavioural tests. The zebrafish is a popular model organism for biological and medical research. So far, however, it has not been an obvious research object for the study of psychiatric disorders. This may be about to change.
"These mutant fish behaved very strangely when we moved them to a new aquarium," reports Herwig Baier. All animals experience stress upon moving to an unfamiliar environment. Being separated from members of their own species places the fish under added pressure. Zebrafish initially act withdrawn in this situation and swim around very hesitantly in the first few minutes. But ultimately, curiosity prevails, and they begin to investigate their new tank. However, the fish with the mutation had a particularly strong reaction to the isolation: they sank to the bottom of the tank and stayed completely still. They took an exceptionally long time to get used to the new environment.
An analysis of these "lethargic" fish showed that they had an extremely elevated concentration of the stress hormones cortisol, CRH and ACTH. "We therefore postulated that these fish were suffering from chronic stress and were exhibiting certain aspects of depressive or perhaps hyper-anxious behaviour," says Baier. To put this assumption to the test, the scientists added the antidepressant fluoxetine (marketed under the trade name Prozac, among others) to the water. Shortly afterwards, the fish's behaviour returned to normal.
What was it that made these fish so different? The scientists uncovered a mutation in the glucocorticoid receptor, which is present in almost all of the body's cells and which binds the hormone cortisol. Normally, when cortisol is bound to this receptor it restricts the release of the stress hormones CRH and ACTH. It is this regulating mechanism that enables humans and many animal species to cope with stress. In the type of fish the scientists examined, however, the glucocorticoid receptor was unable to function, and so the level of stress hormones remained high.
"Although there are a whole range of drugs available for depression, no one yet knows what the relationship is between their effect and the stress hormones," explains Herwig Baier. "Our findings provide the first evidence of a possible connection." Understanding the molecular and neurobiological relationships between stress regulation and affective disorders is important in the search for new treatments and drugs. The scientists' discovery is therefore also of interest to the pharmaceutical industry, given that the zebrafish could turn out to be a good model organism for a large-scale screen for new drugs.
ContactProf. Dr. Herwig Baier
Prof. Dr. Herwig Baier | EurekAlert!
Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland
Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy