New clues about the link between stress and depression

Date:
October 2, 2020
Source:
Karolinska Institutet
Summary:
Researchers have identified a protein in the brain that is important
both for the function of the mood-regulating substance serotonin
and for the release of stress hormones, at least in mice. The
findings may have implications for the development of new drugs
for depression and anxiety.



FULL STORY ========================================================================== Researchers at Karolinska Institutet in Sweden have identified a
protein in the brain that is important both for the function of the mood-regulating substance serotonin and for the release of stress
hormones, at least in mice. The findings, which are published in the
journal Molecular Psychiatry, may have implications for the development
of new drugs for depression and anxiety.


========================================================================== After experiencing trauma or severe stress, some people develop an
abnormal stress response or chronic stress. This increases the risk
of developing other diseases such as depression and anxiety, but it
remains unknown what mechanisms are behind it or how the stress response
is regulated.

The research group at Karolinska Institutet has previously shown that a
protein called p11 plays an important role in the function of serotonin,
a neurotransmitter in the brain that regulates mood. Depressed patients
and suicide victims have lower levels of the p11 protein in their
brain, and laboratory mice with reduced p11 levels show depression-
and anxiety-like behaviour. The p11 levels in mice can also be raised
by some antidepressants.

The new study shows that p11 affects the initial release of the stress
hormone cortisol in mice by modulating the activity of specific neurons
in the brain area hypothalamus. Through a completely different signalling pathway originating in the brainstem, p11 also affects the release of
two other stress hormones, adrenaline and noradrenaline. In addition,
the tests showed that mice with p11 deficiency react more strongly to
stress, with a higher heart rate and more signs of anxiety, compared to
mice with normal p11 levels.

"We know that an abnormal stress response can precipitate or worsen
a depression and cause anxiety disorder and cardiovascular disease,"
says first author Vasco Sousa, researcher at the Department of Clinical Neuroscience, Karolinska Institutet. "Therefore, it is important to find
out whether the link between p11 deficiency and stress response that
we see in mice can also be seen in patients." The researchers believe
that the findings may have implications for the development of new,
more effective drugs. There is a great need for new treatments because
current antidepressants are not effective enough in many patients.

"One promising approach involves administration of agents that enhance localised p11 expression, and several experiments are already being
conducted in animal models of depression," says Per Svenningsson,
professor at the Department of Clinical Neuroscience, Karolinska
Institutet, who led the study.

"Another interesting approach which needs further investigation involves developing drugs that block the initiation of the stress hormone response
in the brain."

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


========================================================================== Journal Reference:
1. Vasco C. Sousa, Ioannis Mantas, Nikolas Stroth, Torben Hager,
Marcela
Pereira, Haitang Jiang, Sandra Jabre, Wojciech Paslawski, Oliver
Stiedl, Per Svenningsson. P11 deficiency increases stress reactivity
along with HPA axis and autonomic hyperresponsiveness. Molecular
Psychiatry, 2020; DOI: 10.1038/s41380-020-00887-0 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201002105749.htm

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