When severe infection causes long-term mood disorders: A promising
avenue to prevent mental illness following a transient infection

Date:
April 20, 2022
Source:
Institut Pasteur
Summary:
Scientists used pharmacogenetic techniques to identify a dedicated
neural circuit comprising the central nucleus of the amygdala and
the bed nucleus of the stria terminalis. The activation of this
circuit in the first few hours of sepsis induces anxious behavior
two weeks after the infection has cleared. This behavior observed
in mice mimics the post- traumatic stress disorder observed in
patients recovering from sepsis.



FULL STORY ==========================================================================
The brain is able to detect and regulate localized or systemic
inflammation by using two communication pathways. The first, humoral,
makes use of specific brain structures that enable circulating
inflammatory mediators to enter the brain. The second, neural, involves
nerves whose sensory afferents transmit the inflammatory signal detected
at local level.


==========================================================================
The vagus nerve therefore uses identified receptors to detect a digestive
or lung inflammation. Specific brain structures and networks perceive
and integrate these humoral and neural messages and orchestrate a
regulatory response involving neuroendocrine, neurovegetative and
behavioral elements.

These corrective interventions are controlled respectively by the
hypothalamus and the hypophysis -- the autonomic nervous system and the
limbic system.

Neuroendocrine activation is characterized by the release of cortisol,
the main stress hormone. The autonomic response involves the combined activation of the sympathetic and vagal systems, with the latter believed
to induce a local anti- inflammatory response. Behavioral changes
affect mood, attention, sleep and appetite. The aim of the overall
response is to control inflammation so as to preserve bodily integrity,
or homeostasis. But in some circumstances, it can be ill adapted and
can lead to immunological and/or psychological disorders.

A severe infection known as sepsis is the most common condition capable
of inducing this defense strategy against inflammatory stress. Sepsis
is the leading cause of death worldwide and represents a major public
health challenge. What makes the situation worse is that sepsis is
also associated with chronic psychological disorders such as anxiety, depression and post- traumatic stress disorder. These conditions
significantly increase suicide risk and have a lasting impact on the
personal, social and professional lives of patients. "No preventive
treatments have so far been demonstrated to be effective, probably because
of a lack of understanding of the pathophysiology of these disorders, especially the neural networks implicated in their onset," explains
Professor Tarek Sharshar, Head of the Sainte-Anne Neurology Department.

In an experimental study published in the journal Brain, a team of
scientists from the Institut Pasteur (Perception and Memory laboratory)
and clinicians from the Paris Psychiatry and Neurosciences University
Hospital Group (GHU) (Neurological Resuscitation Department) used pharmacogenetic techniques to identify a dedicated neural circuit
comprising the central nucleus of the amygdala and the bed nucleus of
the stria terminalis. The activation of this circuit in the first few
hours of sepsis induces anxious behavior two weeks after the infection
has cleared. This behavior observed in mice mimics the post-traumatic
stress disorder observed in patients recovering from sepsis.

"This discovery paves the way for new therapeutic strategies for sepsis:
we observed that administering an agent capable of preventing the hyperactivation of this circuit reduces the risks of developing anxiety disorders," explains Professor Pierre-Marie Lledo, Institut Pasteur and
CNRS. This effect is thought to be partly linked with reduced activation
of the vagal afferent integration center.

This study is of particular interest because it identifies both a
dedicated circuit for post-sepsis anxiety and a potential pharmacological treatment. The latter will soon be tested in a multicenter randomized therapeutic trial. By revealing the link between neuroinflammation and psychiatric disorders, this research resonates with the current context
of the COVID-19 pandemic and long COVID.


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


========================================================================== Journal Reference:
1. Lena Bourhy, Aure'lien Mazeraud, Luis H. A. Costa, Jarod Levy,
Damien
Rei, Este'ban Hecquet, Ilana Gabanyi, Fernando A. Bozza, Fabrice
Chre'tien, Pierre-Marie Lledo, Tarek Sharshar, Gabriel Lepousez.

Silencing of amygdala circuits during sepsis prevents the
development of anxiety-related behaviours. Brain, 2022; DOI:
10.1093/brain/awab475 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220420092153.htm

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