ArticlePsychoneuroendocrinology2018
A peripheral immune response to remembering trauma contributes to the maintenance of fear memory in mice.
Article in Psychoneuroendocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- Sex-specific role of microglia in ΔNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Neuroimmune mechanisms in PTSD: inflammatory heterogeneity, circuit dysfunction, and biomarker-based subtypes.Molecular biology reports · 2026Review
- Post-traumatic stress disorder and cardiometabolic dysfunction: Molecular mechanisms and therapeutic targets.iScience · 2026Review
- Association between steatotic liver disease and post-traumatic stress symptoms in the Fukushima health management survey.Scientific reports · 2026Article
- Tracking conditioned fear in pair-housed mice using deep learning and real-time cue delivery.Neurobiology of stress · 2025Article
- Post-traumatic stress disorder: the role of the amygdala and potential therapeutic interventions - a review.Frontiers in psychiatry · 2024Review
- "NO" Time in Fear Response: Possible Implication of Nitric-Oxide-Related Mechanisms in PTSD.Molecules (Basel, Switzerland) · 2023Review
- Sex-specific immune mechanisms in PTSD symptomatology and risk: A translational overview and perspectives.Brain research bulletin · 2023Review
- The NLRP3 Inflammasome in Stress Response: Another Target for the Promiscuous Cannabidiol.Current neuropharmacology · 2023Review
- Immunization with a heat-killed preparation of Mycobacterium vaccae NCTC 11659 enhances auditory-cued fear extinction in a stress-dependent manner.Brain, behavior, and immunity · 2023Article
- Trauma and Remembering: From Neuronal Circuits to Molecules.Life (Basel, Switzerland) · 2022Review
- Decoding Shared Versus Divergent Transcriptomic Signatures Across Cortico-Amygdala Circuitry in PTSD and Depressive Disorders.The American journal of psychiatry · 2022Article
- C-Reactive Protein: Marker of risk for post-traumatic stress disorder and its potential for a mechanistic role in trauma response and recovery.The European journal of neuroscience · 2022Review
- Inflammation-driven brain and gut barrier dysfunction in stress and mood disorders.The European journal of neuroscience · 2022Review
- Neuroimmune mechanisms in fear and panic pathophysiology.Frontiers in psychiatry · 2022Review
- Rapidly GrowingInternational journal of molecular sciences · 2021Review
- Modeling Neuroimmune Interactions in Human Subjects and Animal Models to Predict Subtype-Specific Multidrug Treatments for Gulf War Illness.International journal of molecular sciences · 2021Article
- Neuroimmune Mechanisms as Novel Treatment Targets for Substance Use Disorders and Associated Comorbidities.Frontiers in neuroscience · 2021Review
- A time-dependent contribution of hippocampal CBBritish journal of pharmacology · 2020Article
- Dynamic Patterns of Threat-Associated Gene Expression in the Amygdala and Blood.Frontiers in psychiatry · 2018Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Alterations in peripheral immune markers are observed in individuals with post-traumatic stress disorder (PTSD). PTSD is characterized in part by impaired extinction of fear memory for a traumatic experience. We hypothesized that fear memory extinction is regulated by immune signaling stimulated when fear memory is retrieved. The relationship between fear memory and the peripheral immune response was tested using auditory Pavlovian fear conditioning in mice. Memory for the association was quantified by the amount of conditioned freezing exhibited in response to the conditioned stimulus (CS), extinction and time-dependent changes in circulating inflammatory cytokines. Brief extinction training with 12 CS rapidly and acutely increased circulating levels of the cytokine interleukin-6 (IL-6), downstream IL-6 signaling, other IL-6 related pro-inflammatory cytokines. Transgenic manipulations or neutralizing antibodies that inhibit IL-6 activity did not affect conditioned freezing during the acquisition of fear conditioning or extinction but significantly reduced conditioned freezing 24 h after extinction training with 12 CS. Conversely, conditioned freezing after extinction training was unchanged by IL-6 inhibition when 40 CS were used during the extinction training session. In addition to effectively diminishing conditioned freezing, extinction training with 40 CS also diminished the subsequent IL-6 response to the CS. These data demonstrate that IL-6 released following fear memory retrieval contributes to the maintenance of that fear memory and that this effect is extinction dependent. These findings extend the current understanding for the role of the immune system in PTSD and suggest that IL-6 and other IL-6 related pro-inflammatory cytokines may contribute to the persistence of fear memory in PTSD where fear memory extinction is impaired.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.