Ultrasound causes depression in rodents

An international team of scientists with the participation of specialists from the M.V. Lomonosov, using ultrasound, caused emotional stress in mice and studied its physiological consequences. Changes characteristic of depressive disorders were recorded in the organisms of animals. The results of the work were published in the journal Progress in Neuropsychopharmacology & Biological Psychiatry .  

Scientists define emotional stress as a type of psychological stress that occurs under the influence of emotionogenic factors. It can manifest itself in the form of anxiety and depression, as well as lead to the development of mental illness. Previously, it was believed that emotional stress is an exclusively human trait; it has not been possible to model it on animals. For the same reason, the physiological consequences of this type of stress have been studied extremely poorly.

“Our study broadens the understanding of rodent modeling of depressive disorders with non-invasive approaches based on naturalistic stimuli. We considered the ultrasonic stress of rodents as a model of information stress for people living in large cities and in a state of chronic information uncertainty. Since psychoemotional diseases are more and more often registered among residents of modern large cities, further study of this protocol will allow us to assess the role of emotional stress in affective disorders, – says the lead author of the study, Dmitry Pavlov from Moscow State University. “This is critically important for the development of targeted therapy for a wide range of psychoemotional diseases associated with the influence of an information-rich environment on residents of modern megacities.”

To simulate emotional stress in mice, animals from the experimental group were exposed to ultrasound at different frequencies. Animals from the control group lived in identical conditions, only without ultrasound exposure. After three weeks of the experiment, the scientists performed behavioral tests and detected biochemical changes in their bodies.

Ultrasound plays an important role in the communication of many animals. So, in rodents, ultrasound with a frequency of 20-25 kHz corresponds to danger signals, a frequency of 25-45 kHz is characteristic of neutral signals. Sounds with a frequency higher than 50 kHz have been noted in communication between female and cubs, and some characteristic signals in this frequency range are considered laughter in rats and mice. To create stressful conditions, the scientists used suddenly alternating sounds with frequencies of 20-25 kHz and 25-40 kHz, which sound like “ultrasonic white noise.”

Behavioral tests have shown that ultrasound causes emotional stress in mice. The mice from the experimental group were more anxious and aggressive, showing signs of depression. According to scientists, in animals, under the influence of ultrasound, the expression of genes associated with the production of serotonin, one of the main hormones responsible for pleasure and the daily cycles of sleep and wakefulness, changed. It is known that when the metabolism of serotonin is disturbed, sleep disturbances occur, and depression develops.

After a series of behavioral tests, researchers looked in the brain for biochemical markers of depression and stress. The researchers found that the hippocampus of stressed mice had fewer cells containing the proteins Ki67 and doublecortin (DCX) responsible for neurogenesis . The density of cells containing ionized calcium-binding factor 1 (Iba-1) was, on the contrary, increased, which is usually the case with injuries or brain diseases. The level of expression of a number of genes responsible for the synthesis of proteins that protect neurons and promote the formation of new nerve cells was reduced. In particular, the changes affected the genes of the brain neurotrophic factor (BDNF), its receptor TrkB , as well as anti- apoptotic protein kinase B phosphorolated at serine 473.

In addition to changes in the level of gene expression in mice from the experimental group, the content of proinflammatory signaling molecules in the brain tissues and plasma was increased : interleukin-1β (IL-1β) and interleukin-6. The activity of the enzyme glycogen synthakinase 3, which is associated with the development of Alzheimer’s disease, type II diabetes mellitus and bipolar disorder, has also been increased. Taken together, all of the listed molecular signs indicate the start of inflammatory processes and a decrease in the rate of formation of new neurons and nerve connections.

Similar molecular changes occur in the brain in depressive disorder. Thus, using ultrasound, neuroscientists for the first time have recreated an animal model of emotional stress. This model can be further applied to the search and testing of new drugs and a deeper study of the mechanisms of emotional stress.

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