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Experiments done using the human stem cells have successfully identified the glucocorticoid receptor (GR) which is responsible for the action of antidepressant drugs.

The Glucocorticoid Receptor Responsible for the Action of Antidepressants has been Identified

Prior studies had demonstrated that all classes of antidepressant drugs, like the tricyclics and selective serotonin reuptake inhibitors (SSRIs) are effective by virtue of their ability to produce new brain cells. But the mechanism by which these antidepressants achieved this objective was not clear. There was evidence that the medicines activate genes responsible for releasing nerve growth factor in the neurons. The growth factor helps in the formation of new nerve cells, and as new connections between these nerve cells develop, the person regains behavioral flexibility and his mood is uplifted.

Now, researchers from the Institute of Psychiatry, Kings College, working on stem cells from the hippocampus region of the brain, have reported in the journal of Molecular Psychiatry that it is the Glucocorticoid Receptors that are activated by the antidepressant medicines. The GR, in turn, switch on the genes which are responsible for the generation of new nerve cells. All different types of antidepressants are dependant on the GR to create new neurons.

According to Christoph Anacker, Ph.D., who led the study, identification of the GR as an important factor in the development of new nerve cells will pave way for testing new chemical compounds in the laboratory and help in producing more effective anti depressants with a more specific mechanism of action.

As Antidepressants Work by Stimulating Production of New Neurons, There’s a Delay in Their Onset of Action

Depression is a common phenomenon around the world, effecting about 121 million people. It is known to cause disability and according to the WHO, less than 25% people affected by it have an access to treatment.

Neurogenesis, a process by which new brain cells develop, is reduced in patients suffering from depression. This results in the incapacitating psychological symptoms of depression, like memory loss and low mood. The various antidepressant medicines stimulate the birth of neurons in the hippocampus. Chronic stress, anxiety and depression have been attributed to loss of the neurons of the hippocampus. Blocking the formation of new neurons in the hippocampus of mice resulted in loss of efficacy of the antidepressant medicines. This further corroborates that hippocampal neurogenesis has an important role to play in uplifting the mood.

According to Hen, a grantee of NIH’s National Institute of Mental Health (NIMH) and National Institute on Drug Abuse (NIDA), as antidepressants work by stimulating production of new neurons, there’s a delay in their onset of action. The stem cells in the hippocampus region of brain divide, differentiate, reach their specific positions and establish connections with other neurons. The whole process may take several weeks to be accomplished, and that is the time delay between the taking of antidepressants and their onset of action.

Earlier, it was believed that it was the different neuro- transmitters, like serotonin, dopamine and norepinephrine, which were solely responsible for depression. But now, the identification of the glucocorticoid receptor, responsible for the activation of genes which turn immature hippocampal stem cells into adult brain cells and the resultant relief from depression, has opened up exciting new frontiers in the field of pharmacy.

  • Hara Estroff Marano. How Do Antipressants Work? Published on January 03, 2003 - last reviewed on April 24, 2009. Psychology Today.
  • Luca Santarelli et. all. Creation of New Neurons Critical to Antidepressant Action in Mice. August, 2003. National Insitutute of Mental Health.
  • Kate Kelland. April, 2011. Study reveals new target for antidepressants. Reuters.
  • Photo courtesy of The Mighty Tim Inconnu by Flickr :