[Molecular Biological Aspects of Depressive Disorders: A Modern View].

Depression is a serious mental disorder that affects more than 300 million people worldwide. Due to the lack of effective treatment methods, the pathogenesis of depression is necessary to study in order to understand its development and find new therapies. The review describes the main mechanisms of depression, including the monoamine hypothesis, impairment of the hipotalamic-pituitary-adrenal axis, decreased production of neurotropic factors, and neuroinflammation. Genetic correlations, gene polymorphisms, and epigenetic mechanisms are also considered. Common and different features of the etiology are analyzed for depression and depressive conditions associated with other pathologies (schizophrenia, Parkinson disease, and Alzheimer's disease). Modern experimental methods used to investigate the molecular mechanisms of depressive conditions are described with a focus on gene knockouts in laboratory animals and the CRISPR/Cas technology. Consideration is given to optogenetic and chemogenetic methods and analyses of genetic polymorphisms and their combinations. The data may provide for a better integral understanding of the modern ideas about the pathogenesis of depression as an isolated or comorbid disorder and the prospects in studying the mechanisms of depressive conditions.

Chronic Exposure to Ultrasonic Frequencies Selectively Increases Aggression in Rats.

We studied aggression in male Sprague-Dawley rats in a model of a depressive-like state induced by unpredictable treatment with ultrasonic waves with the frequencies of 20-45 kHz for 1, 2 or 3 weeks. We did not find any increase in the number of animals exhibiting aggression in the "resident-intruder" test after the treatment of any selected duration. However, the aggressive animals exposed to ultrasound exhibited the substantially increased number of attacks and their total duration as well as decreased latency of the first attack compared to the respective indices in the animals of the control group. Taking this into account, it is possible to suggest that the initial level of aggression increases in a model of ultrasonic chronic stress.

Effect of Electroconvulsive Therapy on Cognitive Functions of Rats with Depression-Like Disorders Induced by Ultrasound Exposure.

We studied the effect of electroconvulsive therapy on cognitive functions in rats with depression-like disorder caused by exposure to ultrasound of varying frequency (20-45 kHz). Object recognition and Morris water-maze tests revealed no negative effects of the therapy on memory. Moreover, positive effect of therapy was demonstrated that manifested in amelioration of memory disturbances in depression-like disorders in these behavioral tests. The results of this study do not support the idea about side effects of electroconvulsive therapy, in particular, development of transient amnesia, and are a prerequisite for a more thorough study of internal mechanisms of the effect of the therapy on cognitive sphere.

Effects of Chronic Exposure to Ultrasound of Alternating Frequencies on the Levels of Aggression and Anxiety in CBA and BALB/c mice.

Stress-induced changes in the behavior of CBA and BALB/c mice were studied after 3-week ultrasound exposure (22-45 kHz). The mice of both lines demonstrated increased aggression in the resident-intruder and social interest paradigms and reduced number of social interactions in the social interest test. Elevated plus maze test showed a decrease in anxiety level in CBA mice and an increase in this parameter in BALB/c mice. Chronic exposure to ultrasound induced an increase in aggression level in mice of both lines that was not directly related to changes in anxiety level.

Dynamics of the Development of Depressive-Like State in Rats Stressed by Chronic Exposure of Ultrasound of Variable Frequency.

We studied the effect of ultrasonic waves with a frequency of 20-45 kHz on behavioral reactions of rats after 7, 14 and 21 days of continuous exposure. A decrease in the number of social contacts in the social interest test was recorded in all groups, while lengthening of immobility time in Porsolt test was found only in the groups exposed to ultrasound for 2 and 3 weeks. Memory impairment in the new object recognition test was recorded only after 21 days of stressing. Chronic exposure to ultrasound of variable frequencies leads to the development of a depressive-like state in rats and the duration of exposure affects the specificity of the observed disorders. Different protocols of using of this model help to determine the stages of depressive-like condition in rats that can serve as a basis for the development of new methods of depressive disorders treatment.