Continual stress? Zebrafish to the rescue

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Chronic stress? Zebrafish to the rescue

Photo credit: Pixabay / CC0 Public Domain

A team of researchers led by MIPT's Allan Kalueff has studied chronic stress in zebrafish and found that the animal can serve as a valuable model species for research into related brain diseases, complementing research currently being carried out on rodents. The paper was published in Scientific Reports.

Translation model

The zebrafish, also known as danio rerio, is a freshwater fish belonging to the minnow family. It gets its name for the stripes on its body. Zebrafish are widely used as a translational model in genetics, molecular biology, embryology, pharmacology, and, more recently, neurobiology. Their use as laboratory animals was developed by the American biologist George Streisinger in the 1960s.

The zebrafish offers a number of advantages over other vertebrates. It shows rapid embryonic development that goes from an egg to a larva in just three days. It is quite large, tough and resilient, besides being transparent and developing outside of the mother's body, which allows for easier observation and manipulation. Many internal organs of the zebrafish, especially the cardiovascular system, function in a similar way to humans, and this also applies to the signaling pathways. Overall, we share 87% of our genome with zebrafish. All of this enables biomedical researchers to transfer their findings from zebrafish to humans, enabling reliable studies on drug toxicity and more.

Zebrafish have become a popular model animal in neurobiology, as both juveniles and adult fish have quite complex behavior. The research team, led by Kalueff, partnered with biologists from St. Petersburg State University (SPbU) and Almazov National Medical Research Center, Russia, to model the persistent chronic stress on zebrafish and identify the molecular changes in the body that are associated with associated with this disease. The study showed that zebrafish are an adequate translational model for studying complex neurobiological conditions. The scientists also collected data that might prove useful to those developing treatment options for patients with chronic stress.

Five weeks of stress, then treatment

Increasing evidence from research on mental disorders suggests that it is a risk factor that contributes to the development of other serious and sometimes incurable pathologies. This prompts scientists to study the nature of these diseases and how they develop.

In the study reported in this story, neurobiologists modeled chronic unpredictable stress lasting five weeks. The team stressed a group of laboratory fish by unexpectedly bothering them and monitored the complex behavioral response. Eventually the zebrafish were diagnosed with a fear-like condition and a serotonin metabolic deficit.

"The fact that the drug had a beneficial effect in fish does not directly lead to the same reaction in humans. It is necessary to conduct many experiments and use a range of test systems to prove that the zebrafish is indeed an appropriate type of translation for the transfer, such knowledge is for humans ", commented Allan Kalueff, main researcher of the study and leading researcher at the MIPT laboratory for cell and molecular biology and neurobiology; an SPbU professor. "Our study has shown that it is possible to induce sustained chronic unpredictable stress in zebrafish, with the condition confirmed by all available methods of evidence-based and molecular biology. This means that Danio rerio is susceptible to stress and exhibits similar behavioral symptoms like those observed in higher species. "

The stressed zebrafish in the study were given a common antidepressant called fluoxetine for 11 days, closely monitoring the resulting neurochemical and behavioral changes. The drug reduced symptoms, and its effects were also confirmed by transcriptomic, behavioral and biochemical analyzes.

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More information:
Konstantin A. Demin et al., Understanding the Complex Dynamics of Behavioral, Neurochemical, and Transcriptomic Changes Induced by Persistent Chronic Unpredictable Stress in the Zebrafish, Scientific Reports (2020). DOI: 10.1038 / s41598-020-75855-3

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Moscow Institute of Physics and Technology

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