Cited by 566Neuroinflammation and Neurodegeneration MechanismsTryptophan and brain disordersImmune Response and Inflammation

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Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1β and anti-inflammatory IL-10 cytokines

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Henry, Christopher J., Huang, Yan, Wynne, Angela M., Godbout, Jonathan P.·2009·Brain, Behavior, and Immunity

DOI 10.1016/j.bbi.2008.09.002PMC PMC2692986

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Abstract

In the elderly, systemic infection is associated with an increased frequency of behavioral and cognitive complications. We have reported that peripheral stimulation of the innate immune system with lipopolysaccharide (LPS) causes an exaggerated neuroinflammatory response and prolonged sickness/depressive-like behaviors in aged BALB/c mice. Therefore, the purpose of this study was to determine the degree to which LPS-induced neuroinflammation was associated with microglia-specific induction of neuroinflammatory mediators. Here, we show that peripheral LPS challenge caused a hyperactive microglial response in the aged brain associated with higher induction of inflammatory IL-1beta and anti-inflammatory IL-10. LPS injection caused a marked induction of mRNA expression of both IL-1beta and IL-10 in the cortex of aged mice compared to adults. In the next set of studies, microglia (CD11b(+)/CD45(low)) were isolated from the brain of adult and aged mice following experimental treatments. An age-dependent increase in major histocompatibility complex (MHC) class II mRNA and protein expression was detected in microglia. Moreover, peripheral LPS injection caused a more pronounced increase in IL-1beta, IL-10, Toll-like receptor (TLR)-2, and indoleamine 2,3-dioxygenase (IDO) mRNA levels in microglia isolated from aged mice than adults. Intracellular cytokine protein detection confirmed that peripheral LPS caused the highest increase in IL-1beta and IL-10 levels in microglia of aged mice. Finally, the most prominent induction of IL-1beta was detected in MHC II(+) microglia from aged mice. Taken together, these findings provide novel evidence that age-associated priming of microglia plays a central role in exaggerated neuroinflammation induced by activation of the peripheral innate immune system.

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Authors: Henry, C. J., Huang, Y., Wynne, A. M., & Godbout, J. P.
Affiliations: The Ohio State University (US)
Corresponding author: Godbout, Jonathan P.
ORCID: Huang, Yan
Godbout, Jonathan P.
Venue: Brain, Behavior, and Immunity
Publisher: Elsevier BV
Published: 2009-03
Volume: 23
Issue: 3
Pages: 309-317
ISSN: 0889-1591 (ISSN-L)
DOI: 10.1016/j.bbi.2008.09.002
PMC: PMC2692986
OpenAlex: W2159822434
Cited by: 565
References: 63
Citations by year: 2026: 22 · 2025: 23 · 2024: 26 · 2023: 26 · 2022: 35 · 2021: 39 · 2020: 38 · 2019: 29 · 2018: 42 · 2017: 36 · 2016: 47 · 2015: 41 · 2014: 40 · 2013: 38 · 2012: 33
FWCI: 11.00
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Brain Behavior and Immunity (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute on Aging (R01AG033028)
National Institute of Mental Health (R21MH077817)
National Institute of Allergy and Infectious Diseases (R32-AI-05-5411)
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: lipopolysaccharide challenge, neuroinflammation, aging, IL-1β, IL-10, MHC class II, TLR2, indoleamine 2,3-dioxygenase, microglia, cognitive aging, depression-like behavior, systemic infection
MeSH terms: Aging, Analysis of Variance, Animals, Brain, Cerebral Cortex, Enzyme-Linked Immunosorbent Assay, Gene Expression Regulation, Injections, Intraperitoneal, Lipopolysaccharides, Male, Mice, Inbred BALB C, RNA, Messenger, Polymerase Chain Reaction, Interleukin-10, Microglia, Mice, Interleukin-1beta

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Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1β and anti-inflammatory IL-10 cytokines

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