New research identifies genetic targets for stress hormones in the brain

Chronic stress is a well-known cause of mental health disorders. New research has led to a better understanding of how glucocorticoid hormones (“stress hormones”) work in the brain and what their function is. The findings could lead to more effective strategies in the prevention and treatment of mental health disorders.

The study, led by academics at the University of Bristol and published today in Nature Communication, discovered a link between corticosteroid receptors – the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) – and ciliary and neuroplasticity genes in the hippocampus, a region of the brain involved in stress adaptation, l learning and memory.

The aim of the research was to find out which MR and GR genes interact with throughout the hippocampal genome during normal circadian variation and after exposure to acute stress. The research team also wanted to find out if an interaction would lead to changes in the expression and functional properties of these genes.

The study combined advanced next-generation sequencing, bioinformatics and pathway analysis technologies to provide a better understanding of the action of glucocorticoid hormones, via MRs and GRs, on gene activity in the ‘seahorse.

Researchers have discovered a previously unknown link between MR function and eyelashes. Eyelashes are small, hair-like structures that protrude from cell bodies. The efficient function of cilia is vitally important for brain development and ongoing brain plasticity, but how their structure and function is regulated in neurons is largely unknown.

The discovery of the new role of MRI in the structure and function of eyelashes in relation to neuronal development has led to a better understanding of the role of these cellular structures in the brain and may help resolve (developmental) disorders related to eyelashes. in the future.

The team also found that MR and GR interact with many genes involved in neuroplasticity processes, such as neuron-to-neuron communication and learning and memory processes. Some of these genes, however, have been linked to the development of mental health disorders like major depression, anxiety, PTSD as well as schizophrenia spectrum disorders. Therefore, the dysfunction of glucocorticoid hormones, as seen in chronic stress, could have an adverse effect on mental health through their action on these vulnerability genes, offering a potential new mechanism to explain the long-known implication glucocorticoids in the etiology of mental health disorders.

Although more research into the role that glucocorticoid hormones play in regulating these genes is needed, the findings bridge the gap between the long-standing known implication of glucocorticoids in mental health disorders and the existence of genes. vulnerability.

Hans Reul, professor of neuroscience at Bristol Medical School: Translational Health Sciences (THS), said: “This research is a substantial step forward in our efforts to understand how these powerful glucocorticoid hormones work in the brain and what their function is. .

“We hope our findings will trigger further targeted research into the role these hormones play in the etiology of serious mental disorders like depression, anxiety and PTSD.”

The next steps in the research are to study how the action of glucocorticoid hormones via MR and GR on the hippocampal genome changes under conditions of chronic stress and, thanks to a new grant from the BBSRC, the action of glucocorticoids via MR and GR on the genome of the female brain. Very little is known about this area of ​​research in women, as most studies on stress and glucocorticoid hormones have been conducted in men.