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    Home > Biochemistry News > Biotechnology News > Neural circuits of post-septic anxiety in mice

    Neural circuits of post-septic anxiety in mice

    • Last Update: 2022-05-19
    • Source: Internet
    • Author: User
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    French scientists have discovered in an established mouse model of sepsis a specialized neural circuit responsible for producing anxiety-like behaviors that mimic the psychiatric symptoms seen in patients recovering from sepsis


    The experimental study, published in the journal Brain, uncovers a circuit specifically designed to treat post-septic anxiety, and a potential drug therapy that could help treat people with "prolonged COVID" of patients


    The brain has two ways of detecting and regulating systemic or local inflammation: one is by informing specific regions of the brain of inflammatory circulating mediators and other humoral components, and the other is by afferent sensory nerves that detect and transmit local inflammatory signals to the brain


    Specific neural networks sense and integrate humoral and neural information and coordinate defenses through the autonomic and limbic systems, involving neuroendocrine, autonomic, and behavioral elements


    When the neuroendocrine system is activated, the main stress hormone cortisol is released


    This high-level intervention is designed to control inflammation to maintain body integrity (homeostasis)


    Sepsis, defined as "a dysregulated host response to infection", is the most common disease that induces this defense strategy against inflammatory stress


    Even after recovering from sepsis, patients often experience long-term psychiatric symptoms, including anxiety and post-traumatic stress disorder (PTSD), collectively referred to as "post-septic syndrome," the underlying neurobiology of which is unclear


    "To date, no preventive treatment has been shown to be effective, possibly due to a lack of understanding of the pathophysiology of these diseases, especially the neural networks involved in their onset


    In the current study, neurological resuscitation from the laboratory of a team of scientists at the Pasteur Institute in Paris and clinicians at the University of Paris Psychiatry and Neuroscience Hospital Group (GHU) Pharmaceutical and Pharmacogenetics Techniques was used in the present study.


    To assess the neurobiological mechanisms underlying long-term behavioral disturbances after sepsis, the researchers used an established mouse model of sepsis to induce inflammation (peritonitis) of the extensive membrane of the abdominal cavity (peritoneum) by ligation and puncture of the cecum, pouches located in the small intestine and pouch at the junction of the large intestine

    "We found that mice recovering from sepsis further developed anxiety-related behaviors associated with exaggerated fear memories


    Using the neuromodulatory drug levetiracetam or a pharmacogenetic approach based on inhibiting the conditional expression of DREADD (designer-only receptor-activating designer drugs), the investigators temporarily silenced CEA neurons projecting to the vBNST bed (ventral nucleus of the streak terminalis) in the pus acute phase of toxicosis


    The authors showed that these treatments prevented the subsequent development of anxiety-related behaviors in a mouse model of sepsis


    "Suppressing the activation of anxiety circuits in the brain during sepsis may constitute a new preventive approach to prevent psychiatric outcomes following infection," the researchers concluded


    Dr Pierre-Marie Lledo, a professor at the Pasteur Institute and the French National Academy of Sciences and senior author of the study, said: "This discovery paves the way for new treatment strategies for sepsis


    The authors suggest that this effect is partly related to reduced activation of the vagal afferent integration center


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