Inactivation of the Cerebral NFκB Pathway Inhibits Interleukin-1β-Induced Sickness Behavior and c-Fos Expression in Various Brain Nuclei
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The behavioral effects of peripherally administered interleukin-1beta (IL-1beta) are mediated by the production of cytokines and other proinflammatory mediators at the level of the blood-brain interface and by activation of neural pathway. To assess whether this action is mediated by NFkappaB activation, rats were injected into the lateral ventricle of the brain with a specific inhibitor of NFkappaB activation, the NEMO Binding Domain (NBD) peptide that has been shown previously to abolish completely IL-1beta-induced NFkappaB activation and Cox-2 synthesis in the brain microvasculature. NFkappaB pathway inactivation significantly blocked the behavioral effects of intraperitoneally administered IL-1beta in the form of social withdrawal and decreased food intake, and dramatically reduced IL-1beta-induced c-Fos expression in various brain regions as paraventricular nucleus, supraoptic nucleus, and lateral part of the central amygdala. These findings strongly support the hypothesis that IL-1beta-induced NFkappaB activation at the blood-brain interface is a crucial step in the transmission of immune signals from the periphery to the brain that underlies further events responsible of sickness behavior.
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NF-kB mediates cytokine and stress effects on neurogenesis.
“NF-kB is another inflammatory signal transducer that is of great interest to cytokine-induced depressive behavior, and has been shown to mediate cytokine and stress effects on neurogenesis”
From Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications (2013) · cites this paper as Nadjar et al., 2005
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- Authors
- Nadjar, A., Bluthé, R.-M., May, M. J., Dantzer, R., & Parnet, P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- University of Pennsylvania (US)
- Venue
- Neuropsychopharmacology
- Published
- 2005-05-18
- Volume
- 30
- Issue
- 8
- Pages
- 1492-1499
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2040862506
- Cited by
- 120
- References
- 47
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 7 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 9 · 2014: 4 · 2013: 13 · 2012: 7
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion, public-domain)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Fondation pour la Recherche Médicale
- Centre National de la Recherche Scientifique
- Institut National de la Recherche Agronomique
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- NF-κB signaling, IL-1β, sickness behavior, NEMO-binding domain peptide, Fos expression, blood-brain barrier, neuroinflammation, social withdrawal, dietary intake, paraventricular nucleus, supraoptic nucleus, central amygdala
- MeSH terms
- Analysis of Variance, Animals, Behavior, Animal, Body Weight, Brain, Drug Interactions, Eating, Enzyme Induction, Enzyme Inhibitors, Interleukin-1, Male, Social Behavior, Time Factors, Signal Transduction, Gene Expression Regulation, Enzymologic, NF-kappa B, Proto-Oncogene Proteins c-fos, Rats, Wistar, Immobility Response, Tonic, Rats
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