Found a way to reduce seasonal depression

Scientists of the Federal Research Center “Institute of Cytology and Genetics of the SB RAS” have found that if you increase the expression of the 5-HT7 receptor gene, you can reduce the manifestations of seasonal depression. The author of the work announced this at a conference held as part of the OpenBio 2019 forum .  

According to the WHO, depressive disorders are among the four diseases that most often lead to disability or suicide. These conditions affect about 350 million people, and one in five of them suffer from seasonal depression. Statistics show that the incidence of this disease increases with the latitude to the poles (that is, a significant part of the territory of the Russian Federation is at risk).

The mainstay of treatment for seasonal depression is light therapy and antidepressant medication, but only 60-70% of patients respond positively. Scientists usually model depressive-like behavior on animals. The features of the onset and development of these conditions, the mechanisms of drug resistance and treatment strategies are investigated using molecular genetic technologies.

“Special attention is paid to the study of the role of the brain serotonin system, the complexity of which is caused by a large variety of receptors. The last of these was the type 7 receptor, which until recently was the least studied. It is interesting in that it plays a role in maintaining the balance of the serotonin system, and agonists of this receptor are antidepressants, “says Alexander Rodny, junior researcher at the Institute of Cytology and Genetics of the SB RAS.

Researchers at the Serotonin Receptor Neurogenomics Laboratory of the Federal Research Center of ICG SB RAS artificially increased the expression of the 5-HT7 receptor gene. This interference also affected the 5-HT1A receptor, which is believed to be able to block the production of serotonin and, therefore, can provoke the development of depression.

Scientists have created a plasmid carrying the seventh receptor gene linked to a fluorescent protein. Scientists injected the resulting virus into the midbrain of mice. After that, model animals were placed in conditions of short daylight hours for seven weeks (20 hours “night” and four hours “days”; despite the fact that mice are nocturnal animals, disturbance of circadian rhythms causes a depressive-like state in them). After that, the authors of the work conducted behavioral tests – “forced swimming” and “open field”; the latter was intended to exclude the influence of physical activity on the test result.

During the forced swim test, the mouse is placed in a deep container of water. At first, the animal tries to get out, but after a while it stops floundering and freezes, saving strength. Periods of inactivity and activity alternate. Prolonged immobility of the mouse in this test is believed to indicate depressive-like behavior. An “open field” is an open test area, round or square, in which scientists measure the physical activity of a mouse. They measured the amount of time that the animal spent near the walls of the site and in the central zone, as well as the frequency of being in the center. In addition, the total distance covered was taken into account.

“Tests have shown that animals in which the expression of the seventh receptor gene was experimentally increased showed a decrease in depressive-like behavior without changing motor activity,” Rodny notes. “Biochemical indicators of serotonin activity are consistent with the results of behavioral tests.”

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