Novel research identifies gene targets of stress hormones in the brain


Date:
August 6, 2021
Source:
University of Bristol
Summary:
Chronic stress is a well-known cause for mental health
disorders. New research has moved a step forward in understanding
how glucocorticoid hormones ('stress hormones') act upon the
brain and what their function is. The findings could lead to more
effective strategies in the prevention and treatment of mental
health disorders.



FULL STORY ========================================================================== Chronic stress is a well-known cause for mental health disorders. New
research has moved a step forward in understanding how glucocorticoid
hormones ('stress hormones') act upon 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 [6 August] in Nature Communications,has discovered a link between corticosteroid receptors -- the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) -- and ciliary and neuroplasticity genes
in the hippocampus, a region of the brain involved in stress coping and learning and memory.

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

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.

The researchers found a previously unknown link between the MR and
cilia function. Cilia are small hair-like structures that protrude from
cell bodies.

Effective cilia function 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 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 and could help resolve cilia-related (developmental) disorders in the future.

The team also found 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,
however, have been linked to the development of mental health disorders
like major depression, anxiety, PTSD as well as schizophrenia spectrum disorders. Consequently, glucocorticoid hormone dysfunction, as observed
in chronic stress, could have a harmful effect on mental health through
their action on these vulnerability genes, providing a potential new
mechanism to explain the long-known involvement of glucocorticoids in
the aetiology of mental health disorders.

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

Hans Reul, Professor of Neuroscience in 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 act upon the brain and what their function is.

"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." Next steps for the research
include studying how glucocorticoid hormone action via MR and GR on
the hippocampus genome changes under chronic stress conditions and,
thanks to a new BBSRC grant, glucocorticoid action via MR and GR upon
the female brain genome. Very little is known about this research area
in females as most studies on stress and glucocorticoid hormones have
been conducted in males.

The study, supported by the BBSRC and a Wellcome Trust Neural Dynamics
PhD studentship, was carried out by the Neuro-Epigenetics Research
Group led by Professor Hans Reul and Dr Karen Mifsud, in collaboration
with Bristol's Stem Cell Biology Group -- Dr Oscar Cordero Llana and Ms Andriana Gialeli -- and sequencing specialists and bioinformaticians at
the University of Oxford.

========================================================================== Story Source: Materials provided by University_of_Bristol. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. 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. Distinct
regulation of hippocampal neuroplasticity and ciliary genes by
corticosteroid receptors. Nature Communications, 2021; 12 (1) DOI:
10.1038/s41467-021- 24967-z ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210806104334.htm

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