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Researchers from the Hebrew University discovered that the degeneration of the cells of the immune system in the brain leads to the development of depression

The researchers have registered a patent for substances that will enable rapid treatment of depression

Prof. Raz Yeremiah. Photo: The Hebrew University
Prof. Raz Yeremiah. Photo: The Hebrew University

The disease of depression, from which one in six people will suffer during their lifetime, is one of the main causes of human suffering. Besides the fact that most suicide cases are related to depression, the disease is a significant risk for other serious diseases, such as cardiovascular diseases, and according to the World Health Organization causes more years of disability and dysfunction than any other disease.

For decades there has been no significant progress in the development of innovative drug treatments for depression because the biological factors responsible for it are still unclear. Now a joint effort of researchers from the Hebrew University of Jerusalem and the University of Colorado is leading to a significant breakthrough in the field. The researchers discovered for the first time that changes in the structure and function of brain cells called microglia cause the development of behavioral and brain symptoms related to depression that results from exposure to prolonged stress. In addition, the researchers registered a patent for several substances that affect the microglial cells that could be used as effective anti-depressant drugs, through the "application" of the Research Development Society of the Hebrew University.

The study was conducted by Prof. Raz Yeremia, head of the Psychoneuroimmunology Laboratory in the Department of Psychology at the Hebrew University, together with PhD student Tirza Kreisel and other researchers in the laboratory at the Hebrew University and in collaboration with researchers from the University of Colorado in Boulder, USA. The research was funded by the National Science Foundation and was published this week in Molecular Psychiatry, the most important journal in psychiatry and one of the leaders in medicine and neuroscience.

Microglial cells, which make up about ten percent of the brain cells, are the representatives of the immune system in the brain, and play a central role in dealing with disease agents such as viruses and bacteria as well as in dealing with brain damage. In the studies conducted in recent years in the laboratory of Prof. Yeremia and other laboratories, it was found that these cells are also involved in other physiological processes, including reactivity to stressful situations.

Prolonged exposure to stressful situations is one of the main factors in the development of depression in humans. In the present study, mice were exposed daily to unpredictable mild stress situations. After five weeks of this exposure, the mice developed symptoms that parallel symptoms of depressed patients, such as despair, lack of interest in activities that cause pleasure such as drinking sweet solutions or social play, as well as a decrease in the creation of new brain cells which is considered one of the most important brain markers in depression.

The researchers found that during the first week of exposure to stress, the microglial cells underwent activation - an activation process that caused the cells to divide and multiply, increase in cell size and produce inflammatory molecules - which resulted in the death of some of the cells.

After 5 weeks of exposure to stress, the number of microglial cells decreased and some of the remaining cells degenerated, mainly in a certain area of ​​the brain that is known to be involved in reactivity to stressful situations. Blocking the initial activation process of the microglial cells by giving a specific drug in the first days of exposure to stress, or through genetic intervention, stopped both the death of the microglial cells and their disappearance from the brain and the depressive symptoms. On the other hand, in order to treat the "depressed" mice, which have already gone through the prolonged exposure to stress and lost many microglial cells, the researchers discovered that there is a need for substances that stimulate the microglial cells and increase their number to a normal level.

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According to Prof. Jeremiah, "we found that with the help of these substances it is possible to cure the depressive symptoms and increase the process of the formation of new nerve cells in a more effective and faster way than most of the drug treatments available today." The researchers continue to identify additional substances of the same type and plan to test their clinical effectiveness in depressed patients in the near future. "Beyond the practical importance and the clinical possibilities that this research opens up," adds Prof. Yermia, "these results are of great theoretical importance as they constitute primary direct evidence that psychological processes and psychiatric diseases do not only reflect the activity of nerve cells (neurons) and disturbances to this activity, as they thought So far, but they are significantly affected by the function of microglia cells".

On the basis of the research findings, the company "Yasim" filed a patent application for the treatment of depression with the help of several specific substances that activate the microglial cells.

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