CoChat
Sign Up
Cited by 813Neuroinflammation and Neurodegeneration MechanismsTryptophan and brain disordersImmune Response and Inflammation

Exaggerated neuroinflammation and sickness behavior in aged mice after activation of the peripheral innate immune system

Godbout, J. P., Chen, J., Abraham, J., Richwine, A. F., Berg, B. M., Kelley, K. W., Johnson, R. W.·2005·The FASEB Journal
DOI 10.1096/fj.05-3776fje
Open this paper in CoChat — free account

Abstract

Acute cognitive impairment (i.e., delirium) is common in elderly emergency department patients and frequently results from infections that are unrelated to the central nervous system. Since activation of the peripheral innate immune system induces brain microglia to produce inflammatory cytokines that are responsible for behavioral deficits, we investigated if aging exacerbated neuroinflammation and sickness behavior after peripheral injection of lipopolysaccharide (LPS). Microarray analysis revealed a transcriptional profile indicating the presence of primed or activated microglia and increased inflammation in the aged brain. Furthermore, aged mice had a unique gene expression profile in the brain after an intraperitoneal injection of LPS, and the LPS-induced elevation in the brain inflammatory cytokines and oxidative stress was both exaggerated and prolonged compared with adults. Aged mice were anorectic longer and lost more weight than adults after peripheral LPS administration. Moreover, reductions in both locomotor and social behavior remained 24 h later in aged mice, when adults had fully recovered, and the exaggerated neuroinflammatory response in aged mice was not reliably paralleled by increased circulating cytokines in the periphery. Taken together, these data establish that activation of the peripheral innate immune system leads to exacerbated neuroinflammation in the aged as compared with adult mice. This dysregulated link between the peripheral and central innate immune system is likely to be involved in the severe behavioral deficits that frequently occur in older adults with systemic infections.

Integrity signals

Registry

Crossref · 10.1096/fj.05-3776fje

Cites

57 of 57 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Accumulated pro-inflammation and oxidative stress in the brain, often observed in aged brains and aged microglia, could cause sustained suppression of Trem2 expression and thus an impairment of TREM2-dependent microglial functions.

    “accumulated pro-inflammation and oxidative stress in the brain, which is often observed in aged brains and aged microglia (90–94), could cause sustained suppression of Trem2 expression and thus an impairment of TREM2-dependent microglial functions.”

    From <i>Trem2</i> promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [91]

  • The exaggerated expression of cytokines in the aged mice was associated with prolonged sickness and depressive-like behavior.

    “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, 2005

  • Systemic injection of LPS caused an exaggerated and sustained neuroinflammatory response in the aged mice.

    “For instance, systemic injection of LPS caused an exaggerated and sustained neuroinflammatory response in the aged mice (Godbout et al, 2005).”

    From Microglia Priming with Aging and Stress (2017) · cites this paper as Godbout et al, 2005

  • Microglia under normal aging showed upregulation of genes associated with antigen presentation, such as MHCII, CD86, and CIITA, and suppression of anti-inflammatory genes, such as IL-10 and CD200.

    “Microglia under normal aging (ie, aging in absence of neurodegeneration) showed upregulation of genes associated with antigen presentation, such as MHCII, CD86, and CIITA (Frank et al, 2006;Godbout et al, 2005;VanGuilder et al, 2011), and suppression of anti-inflammatory genes, such as IL-10 and CD200 (Frank et al, 2006).”

    From Microglia Priming with Aging and Stress (2017) · cites this paper as Godbout et al, 2005

  • Microarray results from the mice brain also showed an age-associated upregulation of genes that code for lysozyme, complement, MHC proteins, and others implicated in immune function.

    “Corresponding with these data, microarray results from the mice brain also showed an age-associated upregulation of genes that code for lysozyme, complement, MHC proteins, and others implicated in immune function (Godbout et al, 2005).”

    From Microglia Priming with Aging and Stress (2017) · cites this paper as Godbout et al, 2005

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Godbout, J. P., Chen, J., Abraham, J., Richwine, A. F., Berg, B. M., Kelley, K. W., & Johnson, R. W.
Affiliations
University of Illinois Urbana-Champaign (US)
ORCID
Venue
The FASEB Journal
Publisher
Wiley
Published
2005-05-26
Volume
19
Issue
10
Pages
1329-1331
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
DOI
10.1096/fj.05-3776fje
OpenAlex
W2154653323
Cited by
813
References
57
Citations by year
2026: 12 · 2025: 29 · 2024: 27 · 2023: 34 · 2022: 58 · 2021: 63 · 2020: 43 · 2019: 35 · 2018: 60 · 2017: 38 · 2016: 44 · 2015: 51 · 2014: 35 · 2013: 47 · 2012: 41
FWCI
14.89
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The FASEB Journal (publishedVersion)
  • PubMed (publishedVersion)
Funders
Institut National de la Santé et de la Recherche Médicale (AG‐16710, MH‐069148)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
neuroinflammation, aging, sickness behavior, lipopolysaccharide, microglia, brain gene expression, inflammatory cytokines, oxidative stress, anorexia, locomotor behavior, social behavior, delirium, systemic infection, older adults
MeSH terms
Aging, Animals, Brain, Immunity, Innate, Inflammation, Interleukin-1, Lipopolysaccharides, Male, Mice, Inbred BALB C, Motor Activity, Social Behavior, Tumor Necrosis Factor-alpha, Interleukin-6, Microglia, Neurodegenerative Diseases, Gene Expression Profiling, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review