Chronic stress has been linked to a variety of health problems, both physical and mental. Now researchers are learning more about how glucocorticoid hormones and their receptors in the brain and how they're affected by stress. Reporting in Nature Communications, scientists have found that there is a connection between corticosteroid receptors and genes in the hippocampus that involve both neuroplasticity and a signaling structure called the cilium.
The hippocampus is a part of that brain that plays a role in learning, memory, and coping with stress. The mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) are both corticosteroid receptors; they bind to glucocorticoids, a group of steroid hormones that includes hydrocortisone. Primary cilia are small appendages on most cell types that can detect and respond to molecular signals (they're not the same as motile cilia). In recent decades, researchers, including myself, have helped identify important roles for cilia in a variety of pathways and cilia dysfunction in several diseases, now known as ciliopathies.
This study assessed gene expression in the hippocampus that was mediated by glucocorticoids through MR and GR. The researchers found that MRs are linked to the function of cilia.
MR and GR were found to interact with many neuroplasticity genes, some of which are involved in memory or signaling between neurons. Chronic stress is thought to disrupt glucocorticoids; that connection may help explain how these molecules may be causing mental health problems.
Much more work will be needed to understand how glucocorticoids can impact gene expression, especially because female research models have been excluded from a lot of glucocorticoid research. This work can, however, help scientists understand how glucocorticoids are related to mental health disorders and which genes may be involved or confer risk.
“This research is a substantial step forward in our efforts to understand how these powerful glucocorticoid hormones act upon the brain and what their function is," said Hans Reul, Professor of Neuroscience in Bristol Medical School: Translational Health Sciences (THS). “We hope that our findings will trigger new targeted research into the role these hormones play in the etiology of severe mental disorders like depression, anxiety, and PTSD."