• When severe infection causes long-term m

    From ScienceDaily@1:317/3 to All on Wednesday, April 20, 2022 22:30:50
    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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