Better Understanding of How Stress Hormones Work

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Better Understanding of How Stress Hormones Work

Jim Windell

            It’s commonly known that chronic stress can cause mental health disorders. But what is not so well known or understood is how stress hormones work and what exactly their function is.

           A new study conducted by scientists at the University of Bristol has discovered a link between corticosteroid receptors and ciliary and neuroplasticity genes in the hippocampus.

           The aim of the research was to find out what genes the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) interact with across the entire hippocampus genome during normal circadian variation and after exposure to acute stress. The researchers also wanted to discover whether any interaction would result in changes in the expression and functional properties of these genes.

           The corticosteroid receptors are the MR and the GR and are typically referred to as the stress hormones. The cilia are small hair-like structures that protrude from cell bodies. Effective cilia function is thought to be vitally important for brain development and ongoing brain plasticity – but how their structure and function is regulated in neurons is largely unknown. The hippocampus, of course, is a region of the brain involved in stress coping and learning and memory.

           The study combined advanced next-generation sequencing, bioinformatics and pathway analysis technologies to enable a greater understanding into glucocorticoid hormone action, via MRs and GRs, on gene activity in the hippocampus. One of the findings was a previously unknown link between the MR and cilia function. This discovery of the novel role of MR in cilia structure and function in relation to neuronal development has increased knowledge of the role of these cell structures in the brain, which could help resolve cilia-related (developmental) disorders in the future.

           Hans Reul, Professor of Neuroscience in Bristol Medical School: Translational Health Sciences, led the study, and the results were recently published in Nature Communications. Among the other findings was that MR and GR interact with many genes which are involved in neuroplasticity processes, such as neuron-to-neuron communication and learning and memory processes. Some of these genes have been linked to the development of mental health disorders like major depression, anxiety, PTSD as well as schizophrenia spectrum disorders.

           “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 Reul. “We hope that our findings will trigger new targeted research into the role these hormones play in the aetiology of severe mental disorders like depression, anxiety and PTSD.”

            Reul pointed out that although further research on the role glucocorticoid hormones play in the regulation of these genes is needed, the findings help fill the gap between the long-known involvement of glucocorticoids in mental health disorders and the existence of vulnerability genes.

            According to the researchers, next efforts in the ongoing research is to learn more about how glucocorticoid hormone action via MR and GR on the hippocampus genome changes under chronic stress conditions. They would also like to study how glucocorticoid action via MR and GR reacts on the female brain genome. Most previous research on stress and glucocorticoid hormones has been conducted with males, so little is known about this research area in females.

            But for now, as a consequence of this study, scientists have a greater understanding of how stress hormones act on the brain while also better understanding their function. Future research could lead to more effective strategies in the prevention and treatment of mental health disorders.

            To read the original article, find it with this reference:

Karen R. Mifsud, Clare L. M. Kennedy, Silvia Salatino, Eshita Sharma, Emily M. Price, Samantha N. Haque, Andriana Gialeli, Hannah M. Goss, Polina E. Panchenko, John Broxholme, Simon Engledow, Helen Lockstone, Oscar Cordero Llana, Johannes M. H. M. Reul. (2021). Distinct regulation of hippocampal neuroplasticity and ciliary genes by corticosteroid receptors. Nature Communications, 12 (1) DOI: 10.1038/s41467-021-24967-z

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