Cited by 299Tryptophan and brain disordersStress Responses and CortisolNeuroinflammation and Neurodegeneration Mechanisms

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Aging Exacerbates Depressive-like Behavior in Mice in Response to Activation of the Peripheral Innate Immune System

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Godbout, Jonathan P, Moreau, Maïté, Lestage, Jacques, Chen, Jing, Sparkman, Nathan L, Connor, Jason O', Castanon, Nathalie, Kelley, Keith W, Dantzer, Robert, Johnson, Rodney W·2008·Neuropsychopharmacology

DOI 10.1038/sj.npp.1301649PMC PMC2907915

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Abstract

Exposure to peripheral infections may be permissive to cognitive and behavioral complications in the elderly. We have reported that peripheral stimulation of the innate immune system with lipopolysaccharide (LPS) causes an exaggerated neuroinflammatory response and prolonged sickness behavior in aged BALB/c mice. Because LPS also causes depressive behavior, the purpose of this study was to determine whether aging is associated with an exacerbated depressive-like response. We confirmed that LPS (0.33 mg/kg intraperitoneal) induced a protracted sickness response in aged mice with reductions in locomotor and feeding activities 24 and 48 h postinjection, when young adults had fully recovered. When submitted to the forced swim test 24 h post-LPS, both young adult and aged mice exhibited an increased duration of immobility. However, when submitted to either the forced swim test or the tail suspension test 72 h post-LPS, an increased duration of immobility was evident only in aged mice. This prolonged depressive-like behavior in aged LPS-treated mice was associated with a more pronounced induction of peripheral and brain indoleamine 2,3-dioxygenase and a markedly higher turnover rate of brain serotonin (as measured by the ratio of 5-hydroxy-indoleacetic acid over 5-hydroxy-tryptamine) compared to young adult mice at 24 post-LPS injection. These results provide the first evidence that age-associated reactivity of the brain cytokine system could play a pathophysiological role in the increased prevalence of depression observed in the elderly.

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Authors: Godbout, J. P., Moreau, M., Lestage, J., Chen, J., Sparkman, N. L., Connor, J. O., Castanon, N., Kelley, K. W., Dantzer, R., & Johnson, R. W.
Affiliations: Institute for Behavioral Medicine (US)
Centre National de la Recherche Scientifique (FR)
University of Illinois Urbana-Champaign (US)
Corresponding author: Johnson, Rodney W
ORCID: Moreau, Maïté
Chen, Jing
Castanon, Nathalie
Kelley, Keith W
Dantzer, Robert
Johnson, Rodney W
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2007-12-12
Volume: 33
Issue: 10
Pages: 2341-2351
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/sj.npp.1301649
PMC: PMC2907915
OpenAlex: W2001809220
Cited by: 299
References: 64
Citations by year: 2026: 3 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 18 · 2021: 23 · 2020: 12 · 2019: 10 · 2018: 21 · 2017: 13 · 2016: 25 · 2015: 21 · 2014: 17 · 2013: 28 · 2012: 25
FWCI: 5.52
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Neuropsychopharmacology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
HAL (submittedVersion)
Funders: American Federation for Aging Research
National Institutes of Health
National Institute on Aging (AG029573, AG 16710, R01AG016710, R01AG029573)
National Institute of Mental Health (MH071349, MH-079829, R01MH079829, MH 069148, R01MH071349, MH076786, R01MH069148, R03MH076786)
Topics: Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: aging, depression-like behavior, lipopolysaccharide, sickness behavior, neuroinflammation, indoleamine 2,3-dioxygenase, serotonin turnover, 5-hydroxyindoleacetic acid, brain cytokines, geriatric depression, forced swim test, tail suspension test
MeSH terms: Aging, Animals, Behavior, Animal, Brain, Brain Chemistry, Depressive Disorder, Disease Models, Animal, Immunity, Innate, Infections, Inflammation, Lipopolysaccharides, Male, Mice, Inbred BALB C, Motor Activity, Serotonin, Down-Regulation, Cytokines, Inflammation Mediators, Indoleamine-Pyrrole 2,3,-Dioxygenase, Mice, Illness Behavior

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Aging Exacerbates Depressive-like Behavior in Mice in Response to Activation of the Peripheral Innate Immune System

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