---
title: "Vagal Subcircuits Regulate Sepsis-Induced Sickness and Anxiety Behaviors"
id: "pubmed-42658674"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42658674"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42658674/"
doi: "10.1016/j.celrep.2026.117896"
published_at: "2026-08-27T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Vagal Subcircuits Regulate Sepsis-Induced Sickness and Anxiety Behaviors
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42658674
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42658674/)
- **DOI:** [10.1016/j.celrep.2026.117896](https://doi.org/10.1016%2Fj.celrep.2026.117896)
- **Published At:** 2026-08-27T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The brain monitors peripheral immune activity through sensory neurons of the **vagus nerve** whose cell bodies are in the **nodose ganglia** and which project to the brainstem dorsal vagal complex. - This vagal-to-brainstem relay activates neural circuits that produce infection-related behavioral changes collectively termed sickness behavior. - In severe systemic inflammation such as **sepsis**, vagal signaling can contribute to brain dysfunction including persistent **anxiety**-related behaviors. - Using the rodent cecal ligation and puncture (CLP) model of sepsis, investigators combined surgical and chemogenetic gain- and loss-of-function techniques to dissect roles of vagal subcircuits. - Activation of neurons within the **dorsal vagal complex** worsened acute sickness behavior and promoted lasting anxiety-related behavior in survivors. - Activation of upstream **nodose** sensory neurons did not produce the same effects as dorsal vagal complex activation. - Transient inhibition of either nodose neurons or dorsal vagal complex neurons had no reported effect on sepsis-induced behaviors. - Performing a **subdiaphragmatic vagotomy** reduced acute brain activation and partially attenuated anxiety symptoms in sepsis survivors. - The results indicate a complex interplay among peripheral immune signals, vagal subcircuits, and brain regions mediating sickness and anxiety, and they underscore the need for mechanistic insight when developing targeted therapies for sepsis-related neurobehavioral dysfunction. - Details such as precise experimental parameters, quantitative behavioral outcomes, animal numbers, and time courses were not reported in the abstract and therefore are not available in this source.
## Clinical Analysis & Structured Key Points
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Online ahead of print. # Vagal subcircuits differentially regulate sepsis-induced sickness and anxiety-related behaviors [Lena Bourhy](https://pubmed.ncbi.nlm.nih.gov/?term=Bourhy+L&cauthor_id=42658674)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42658674/#full-view-affiliation-1 "Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France; Université Paris Cité, Collège doctoral BioSciences Paris Cité, Paris, France. Electronic address: lena.bourhy@crick.ac.uk."), [Carine Moigneu](https://pubmed.ncbi.nlm.nih.gov/?term=Moigneu+C&cauthor_id=42658674)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42658674/#full-view-affiliation-2 "Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France."), [Alice Dupin](https://pubmed.ncbi.nlm.nih.gov/?term=Dupin+A&cauthor_id=42658674)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42658674/#full-view-affiliation-3 "Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France; Sorbonne Université, École doctorale Cerveau, Cognition, Comportement, Paris, France."), [Esteban Delelis](https://pubmed.ncbi.nlm.nih.gov/?term=Delelis+E&cauthor_id=42658674)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42658674/#full-view-affiliation-2 "Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France."), [Jarod Levy](https://pubmed.ncbi.nlm.nih.gov/?term=Levy+J&cauthor_id=42658674)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42658674/#full-view-affiliation-2 "Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France."), [Pierre-Marie Lledo](https://pubmed.ncbi.nlm.nih.gov/?term=Lledo+PM&cauthor_id=42658674)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42658674/#full-view-affiliation-2 "Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France."), [Tarek Sharshar](https://pubmed.ncbi.nlm.nih.gov/?term=Sharshar+T&cauthor_id=42658674)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42658674/#full-view-affiliation-4 "GHU Paris Psychiatrie Neurosciences, Service hospitalo-universitaire de Neuro-anesthésie réanimation, Paris, France."), [Gabriel Lepousez](https://pubmed.ncbi.nlm.nih.gov/?term=Lepousez+G&cauthor_id=42658674)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42658674/#full-view-affiliation-2 "Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France.") Affiliations Expand ### Affiliations * 1 Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France; Université Paris Cité, Collège doctoral BioSciences Paris Cité, Paris, France. Electronic address: lena.bourhy@crick.ac.uk. * 2 Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France. * 3 Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France; Sorbonne Université, École doctorale Cerveau, Cognition, Comportement, Paris, France. * 4 GHU Paris Psychiatrie Neurosciences, Service hospitalo-universitaire de Neuro-anesthésie réanimation, Paris, France. * PMID: **42658674** * DOI: [ 10.1016/j.celrep.2026.117896 ](https://doi.org/10.1016/j.celrep.2026.117896) Item in Clipboard # Vagal subcircuits differentially regulate sepsis-induced sickness and anxiety-related behaviors Lena Bourhy et al. Cell Rep. 2026. Show details Display options Display options Format Abstract PubMed PMID Cell Rep Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cell+Rep%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Cell+Rep%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42658674/) . 2026 Aug 27;45(9):117896. doi: 10.1016/j.celrep.2026.117896. Online ahead of print. ### Authors [Lena Bourhy](https://pubmed.ncbi.nlm.nih.gov/?term=Bourhy+L&cauthor_id=42658674)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42658674/#short-view-affiliation-1 "Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France; Université Paris Cité, Collège doctoral BioSciences Paris Cité, Paris, France. Electronic address: lena.bourhy@crick.ac.uk."), [Carine Moigneu](https://pubmed.ncbi.nlm.nih.gov/?term=Moigneu+C&cauthor_id=42658674)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42658674/#short-view-affiliation-2 "Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France."), [Alice Dupin](https://pubmed.ncbi.nlm.nih.gov/?term=Dupin+A&cauthor_id=42658674)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42658674/#short-view-affiliation-3 "Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France; Sorbonne Université, École doctorale Cerveau, Cognition, Comportement, Paris, France."), [Esteban Delelis](https://pubmed.ncbi.nlm.nih.gov/?term=Delelis+E&cauthor_id=42658674)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42658674/#short-view-affiliation-2 "Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France."), [Jarod Levy](https://pubmed.ncbi.nlm.nih.gov/?term=Levy+J&cauthor_id=42658674)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42658674/#short-view-affiliation-2 "Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France."), [Pierre-Marie Lledo](https://pubmed.ncbi.nlm.nih.gov/?term=Lledo+PM&cauthor_id=42658674)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42658674/#short-view-affiliation-2 "Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France."), [Tarek Sharshar](https://pubmed.ncbi.nlm.nih.gov/?term=Sharshar+T&cauthor_id=42658674)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42658674/#short-view-affiliation-4 "GHU Paris Psychiatrie Neurosciences, Service hospitalo-universitaire de Neuro-anesthésie réanimation, Paris, France."), [Gabriel Lepousez](https://pubmed.ncbi.nlm.nih.gov/?term=Lepousez+G&cauthor_id=42658674)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42658674/#short-view-affiliation-2 "Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France.") ### Affiliations * 1 Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France; Université Paris Cité, Collège doctoral BioSciences Paris Cité, Paris, France. Electronic address: lena.bourhy@crick.ac.uk. * 2 Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France. * 3 Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Action Unit, Paris, France; Sorbonne Université, École doctorale Cerveau, Cognition, Comportement, Paris, France. * 4 GHU Paris Psychiatrie Neurosciences, Service hospitalo-universitaire de Neuro-anesthésie réanimation, Paris, France. * PMID: **42658674** * DOI: [ 10.1016/j.celrep.2026.117896 ](https://doi.org/10.1016/j.celrep.2026.117896) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract The brain monitors peripheral immune activity via vagus nerve sensory neurons, whose cell bodies lie in the nodose ganglia and project to the brainstem dorsal vagal complex. This relay activates neural circuits mediating infection-related behavioral changes, such as sickness behavior. In severe inflammation like sepsis, this signaling can contribute to brain dysfunction, including persistent anxiety. Using the rodent sepsis model of cecal ligation and puncture, we investigated how vagal subcircuits contribute to these effects, by integrating surgical and chemogenetic gain- and loss-of-function approaches. Activating dorsal vagal complex neurons exacerbated sickness behavior and promoted lasting anxiety-related behavior, while activating upstream nodose neurons did not. Nodose or brainstem transient inhibition had no effect. However, subdiaphragmatic vagotomy reduced acute brain activation and partly attenuated anxiety symptoms in sepsis survivors. These results highlight the complex vagal-immune-brain interplay and emphasize the importance of mechanistic insights to guide the development of targeted therapies. **Keywords:** CP: neuroscience; anxiety; cecal ligation and puncture; dorsal vagal complex; extended amygdala; fear conditioning; neuro-immune interactions; neuroinflammation; nucleus of the tractus solitarius; pharmacogenetics; vagotomy. Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of interests All authors declare no competing interests. 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