In a new study, researchers show that current antidepressant medications regulate or control the glucocorticoid receptor (GR) — a key protein involved in the stress response. Regulation of this receptor is critical as researchers believe antidepressant medications augment creation of new brain cells by the GR.
The Laboratory of Stress, Psychiatry and Immunology (SPI-lab) at King’s College, London, has been looking into the role of the GR in depression for a number of years. In this study, scientists used human hippocampal stem cells, the source of new cells in the human brain, as a new model to investigate “in a dish” the effects of antidepressants on brain cells.
“For the first time in a clinically relevant model, we were able to show that antidepressants produce more stem cells and also accelerate their development into adult brain cells,” noted Christoph Anacker, lead author of the new study and a doctoral student at the Institute of Psychiatry at King’s College.
“We demonstrated for the first time that stress hormones — which are generally very high in depressed patients — show the opposite effect.”
Depressed patients show a reduction in neurogenesis. Experts believe this reduction in new brain cells may contribute to the symptoms of depression, such as low mood or impaired memory.
“We discovered that a specific protein in the cell, the glucocorticoid receptor, is essential for [neurogenesis] to take place,” Anacker said. “The antidepressants activate this protein which switches on particular genes that turn immature ‘stem’ cells into adult ‘brain’ cells.”
By increasing the number of newborn cells in the adult human brain, Anacker said, antidepressants counteract the damaging effects of stress hormones and may overcome the brain abnormalities that may cause mood and memory dysfunction.
Investigators believe the finding will help in the development of new antidepressant medications, an urgent need as half of all depressed patients fail to improve with current treatments.
Anacker concluded: “Having identified the glucocorticoid receptor as a key player in making new brain cells, we will now be able to use this novel stem cell system to model psychiatric illnesses in the laboratory, test new compounds and develop much more effective, targeted antidepressant drugs. However, first it is important that future studies investigate all possible effects that the increase of neurogenesis has on behavior in humans.”
Study findings will be published in the journal Molecular Psychiatry.
Source: King’s College London