07 December 2021

Together with colleagues from the Pavlov Institute of Physiology of the Russian Academy of Sciences, scientists of the Immanuel Kant Baltic Federal University proved that “nervous” rats are more likely than more stable species to develop mental problems due to stress. Stress factors have a more significant impact on their immune system, which leads to an inadequate inflammatory reaction in the brain. This reaction can enable a pathological scenario embedded in genes. This conclusion was reached by the authors after a long-term study of the behavior of two strains of rats that differ in their peripheral and central nervous system excitation. The results were published in the Plos One journal.

Long-term stress is a risk factor for various psychopathologies such as anxiety, depression, bipolar, and other disorders. The exact mechanism is not yet well studied, but there is a theory about the processes which are involved. Stress-induced hormones can adversely affect the immune system. As a result, inflammatory reactions occur. Moreover, the signs of inflammation occur not only in the blood but also in the brain. Disorders of the hypothalamus structures and pituitary glands, changes in gene activity lead to dysfunction of neurons and glia (auxiliary cells of the nervous tissue). It is possible that if there is a genetic predisposition to mental illness, stress will lead to it. Together with colleagues from the Pavlov Institute of Physiology of the Russian Academy of Sciences, scientists of the Immanuel Kant Baltic Federal University decided to test this theory on two strains of rats characterized by different nervous system excitation.

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“Scientists investigate the rats’ mechanisms of stress to use the information for treating humans’ severe psycho-emotional disorders. Rats are mammals, they’re evolutionarily distant from us, but they have quite complex nervous systems, complex behavior, and in many ways, the mechanisms of stress are conservative. Therefore they are similar for rodents and humans. We need to understand that if we discovered the effect of the nervous system excitation on the severity of poststressor inflammation in the rats’ brain, it doesn’t mean that it’s going to be the same with humans. But these conclusions allow us to make assumptions, which can already be tested in the future”, — says Irina Shalaginova, the head of this research, the scientist from the Immanuel Kant Baltic Federal University.

At the Pavlov Institute of Physiology of the Russian Academy of Science, rats have been studied for several decades. They were selected by the level of excitability of the nervous system  Thus, unique animal strains were created — highly excitable ones and low excitable ones. This experiment involved 206 animals from both of these strains. To simulate stress, each day for 15 consecutive days, the subjects were exposed to six unsupported and six current-reinforced light signals. According to the special scheme, combinations of conditional (current) and unconditional (light) irritants were not repeated, but alternating, which did not allow animals to develop a conditional reflex. To avoid the effects of anesthesia on experimental results, scientists had to use the instant decapitation of animals with a guillotine. This manipulation was carried out by an experienced lab technician.

The behavior of rats with a low excitability threshold (high-excitability strain) showed a significant change, in a complex way. One day after the stress, their research behavior declined, which can be interpreted as an increase in anxiety. For example, they were much less likely to enter the center of the labyrinth during tests and spent less time caring for their fur. A week after the experiment began, the symptoms of anxiety disappeared, and 24 days later they reappeared again. Probably it happened due to some compensatory mechanisms, which, alas, are not sufficient under conditions of prolonged stress. Also, the number of microglial cells performing an immune defense function in the brain by initiating an inflammatory reaction in all studied areas of the hippocampus increased a week after exposure to stress. The scientists suggest that their influence may have caused changes in the behavior of rats.

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“Stress can cause very serious disorders and we know that some people are more vulnerable than others. It is necessary to find out which individual (including genetically conditioned) characteristics affect this vulnerability. It is also not clear how stress affects the brain, what exactly happens in the nervous system, which changes the behavior and the psycho-emotional state of a person. These are the questions we are trying to answer. Knowing all this, it will be possible to develop effective methods of treatment and prevention of post-stress pathologies”, — comments Irina Shalaginova.