Vagal subcircuits differentially regulate sepsis-induced sickness and anxiety-related behaviors
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.
Related
- Transcriptomic profiling reveals estradiol and progesterone specific microRNA signatures differentially regulate mRNA targets in vaginal epithelial cells
- Distinct medial septal GABAergic pathways differentially regulate spatial memory and network activity
- Blue and green shade nets differentially regulate organic acid accumulation in citrus fruit
- Semen Components Differentially Regulate Endometrial and Systemic Immune Responses in Goats: Molecular Evidence from Ex Vivo and In Vivo Models
- Brown and white adipocyte like cells derived exosomes differentially regulate stemness, hormone secretion, apoptosis, and lipid metabolism in model cells
BibTeX
@article{bourhy2026vagal,
title = {{Vagal subcircuits differentially regulate sepsis-induced sickness and anxiety-related behaviors}},
author = {Lena Bourhy and Carine Moigneu and Alice Dupin and Esteban Delelis and Jarod Levy and Pierre-Marie Lledo and Tarek Sharshar and Gabriel Lepousez},
journal = {Cell Reports},
year = {2026},
month = sep,
doi = {10.1016/j.celrep.2026.117896},
url = {https://hal.science/hal-05826810v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Vagal subcircuits differentially regulate sepsis-induced sickness and anxiety-related behaviors
AU - Lena Bourhy
AU - Carine Moigneu
AU - Alice Dupin
AU - Esteban Delelis
AU - Jarod Levy
AU - Pierre-Marie Lledo
AU - Tarek Sharshar
AU - Gabriel Lepousez
PY - 2026
DA - 2026/09/22
JO - Cell Reports
DO - 10.1016/j.celrep.2026.117896
UR - https://hal.science/hal-05826810v1
AB - 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.
SN - 2211-1247
SN - 2211-1247
ER -