The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
Aging Exacerbates Depressive-like Behavior in Mice in Response to Activation of the Peripheral Innate Immune System
Open accessAbstract
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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“Although previous studies have identified elevated serum IL-6 and circulating leukocytes in stress disorders, this generally followed either depression diagnosis in humans (4, 25) or controlled stress exposure in rodents (26, 27).”
From Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress (2014) · cites this paper as [27]
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“This exaggerated expression of cytokines in the aged mice was associated with the prolonged sickness (Godbout et al, 2005) and depressive-like behavior (Godbout et al, 2008).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Godbout et al, 2008
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Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene
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Cytokines sing the blues: inflammation and the pathogenesis of depression
Raison, C. L., Capuron, L., & Miller, A. H. (2006) · Trends in Immunology · doi:10.1016/j.it.2005.11.006 · Cited by 3,009
Stress-induced immune dysfunction: implications for health
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Gene expression profile of aging and its retardation by caloric restriction
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Self-citationChronic stress and age-related increases in the proinflammatory cytokine IL-6.
Kiecolt-Glaser, J. K., Preacher, K. J., MacCallum, R. C., Atkinson, C., Malarkey, W. B., & Glaser, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1531903100 · Cited by 1,267 · cited 1×
“…and depression is particularly relevant to an older population that has a high incidence of behavioral and cognitive complications concomitant with proinflammatory conditions (Dentino et al, 1999; Glaser et al, 2003; Kiecolt-Glaser et al, 2003; Mulsant and Ganguli, 1999; Penninx et al, 1999, 2003).”
BackgroundCytokines and major depression
Schiepers, O. J. G., Wichers, M. C., & Maes, M. (2005) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2004.11.003 · Cited by 1,235
Gene-expression profile of the ageing brain in mice
Lee, C.-K., Weindruch, R., & Prolla, T. A. (2000) · Nature Genetics · doi:10.1038/77046 · Cited by 1,055
Systemic infections and inflammation affect chronic neurodegeneration
Perry, V. H., Cunningham, C., & Holmes, C. (2007) · Nature Reviews Immunology · doi:10.1038/nri2015 · Cited by 1,027
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From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395
Self-citationNeuroinflammation: The Devil Is in the Details
DiSabato, D. J., Quan, N., & Godbout, J. P. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13607 · Cited by 1,640
Self-citationRegulation of learning and memory by meningeal immunity: a key role for IL-4
Derecki, N. C., Cardani, A. N., Yang, C. H., Quinnies, K. M., Crihfield, A., Lynch, K. R., & Kipnis, J. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20091419 · Cited by 800
Review: microglia of the aged brain: primed to be activated and resistant to regulation
Norden, D. M., & Godbout, J. P. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2012.01306.x · Cited by 792
Self-citationMicroglia and neurodegeneration: The role of systemic inflammation
Cunningham, C. (2013) · Glia · doi:10.1002/glia.22350 · Cited by 769
Metadata
- 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
- Venue
- Neuropsychopharmacology
- Published
- 2007-12-12
- Volume
- 33
- Issue
- 10
- Pages
- 2341-2351
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- 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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